A Phase 1 interventional study of GSK1795091 and GSK3174998 in Neoplasms, sponsored by GlaxoSmithKline. Completed at 8 sites in 4 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-09-23.
Sponsored by GlaxoSmithKline · Phase 1, Interventional, and Treatment
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GSK1795091 is being developed for administration in combination with other immune system modulators for the treatment of cancers. The study will be conducted in two parts. In Part 1, dose escalation will be performed to identify combination dose levels comprising GSK1795091 with either 24 milligrams (mg) GSK3174998 (Part 1a), 80 mg GSK3359609 (Part 1b), or 200 mg pembrolizumab (Part 1c). One dose level of GSK3174998, GSK3359609, or pembrolizumab with up to 5 dose levels of GSK1795091 are planned for evaluation. In Part 2 (dose-expansion), subjects will receive a single dose level of GSK1795091 as identified based on data from Part 1, in combination with either GSK3174998, GSK3359609, or pembrolizumab.
10,822 studies on the registry are indexed under Neoplasms; 2,325 are open to participants now.
This study's enrollment of 54 is close to the median of 60 across 7,706 interventional studies indexed under Neoplasms.
Browse Neoplasms studies →GlaxoSmithKline is the lead sponsor of 3,650 studies on the registry; 117 are open to participants now.
Of its 265 completed or terminated interventional studies of FDA-regulated products, 241 (91%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Additional Inclusion criteria for Subjects in Part 2a (GSK3174998 expansion) and Part 2b (GSK3359609 expansion):
Additional Inclusion Criteria for Subjects in Part 2c (pembrolizumab expansion):
Exclusion Criteria:
Additional Exclusion Criteria for Subjects in Part 2c
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Measurable disease
The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.
The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
RECIST
The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.
“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECOG performance status
A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.
Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
PD-1, PD-L1 and checkpoint inhibitors
PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.
PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Line of therapy
A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.
“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Brain metastases
Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).
Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
QT and QTc
On an ECG, the QT interval is the time the heart’s lower chambers take to activate electrically and recover in each beat. QTc is that time adjusted for heart rate (QTcF by Fridericia’s formula, QTcB by Bazett’s). Some medicines lengthen it, and a long QTc can raise the risk of a dangerous heart rhythm.
The study may name a correction formula and a limit in milliseconds, often around 450–480.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ECG (electrocardiogram)
A recording of the heart’s electrical activity, taken with stickers on the chest, arms and legs. It takes a few minutes and does not hurt.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Allogeneic and autologous transplant
Stem cell (bone marrow) transplants. Allogeneic uses cells from a donor; autologous uses your own cells, collected earlier and given back.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will be administered GSK1795091 50 nanogram (ng) intravenously (IV) on Days 1 and 8 followed by once weekly administration of GSK1795091 50 ng IV in combination with GSK3174998 24 milligram (mg) administered at 3-week intervals (Q3W) via the IV route until Week 12. From Week 12 onwards, GSK1795091 50 ng IV will be administered in combination with GSK3174998 24 mg at Q3W interval.
Drug: GSK1795091 · Drug: GSK3174998
Participants will be administered GSK1795091 100 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 100 ng IV in combination with GSK3174998 24 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 100 ng IV will be administered in combination with GSK3174998 24 mg at Q3W interval.
Drug: GSK1795091 · Drug: GSK3174998
Participants will be administered GSK1795091 150 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 150 ng IV in combination with GSK3174998 24 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 150 ng IV will be administered in combination with GSK3174998 24 mg at Q3W interval.
Drug: GSK1795091 · Drug: GSK3174998
Participants will be administered GSK1795091 200 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 200 ng IV in combination with GSK3174998 24 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 200 ng IV will be administered in combination with GSK3174998 24 mg at Q3W interval.
Drug: GSK1795091 · Drug: GSK3174998
Participants will be administered GSK1795091 250 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 250 ng IV in combination with GSK3174998 24 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 250 ng IV will be administered in combination with GSK3174998 24 mg at Q3W interval.
Drug: GSK1795091 · Drug: GSK3174998
Participants will be administered GSK1795091 50 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 50 ng IV in combination with GSK3359609 80 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 50 ng IV will be administered in combination with GSK3359609 80 mg at Q3W interval.
Drug: GSK1795091 · Drug: GSK3359609
Participants will be administered GSK1795091 100 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 100 ng IV in combination with GSK3359609 80 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 100 ng IV will be administered in combination with GSK3359609 80 mg at Q3W interval.
Drug: GSK1795091 · Drug: GSK3359609 · Drug: Pembrolizumab
Participants will be administered GSK1795091 150 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 150 ng IV in combination with GSK3359609 80 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 150 ng IV will be administered in combination with GSK3359609 80 mg at Q3W interval.
Drug: GSK1795091 · Drug: GSK3359609
Participants will be administered GSK1795091 200 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 200 ng IV in combination with GSK3359609 80 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 200 ng IV will be administered in combination with GSK3359609 80 mg at Q3W interval.
Drug: GSK1795091 · Drug: GSK3359609
Participants will be administered GSK1795091 250 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 250 ng IV in combination with GSK3359609 80 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 250 ng IV will be administered in combination with GSK3359609 80 mg at Q3W interval.
Drug: GSK1795091 · Drug: GSK3359609
Participants will be administered GSK1795091 50 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 50 ng IV in combination with pembrolizumab 200 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 50 ng IV will be administered in combination with pembrolizumab 200 mg at Q3W interval.
Drug: GSK1795091 · Drug: Pembrolizumab
Participants will be administered GSK1795091 100 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 100 ng IV in combination with pembrolizumab 200 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 100 ng IV will be administered in combination with pembrolizumab 200 mg at Q3W interval.
Drug: GSK1795091 · Drug: Pembrolizumab
Participants will be administered GSK1795091 150 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 150 ng IV in combination with pembrolizumab 200 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 150 ng IV will be administered in combination with pembrolizumab 200 mg at Q3W interval.
Drug: GSK1795091 · Drug: Pembrolizumab
Participants will be administered GSK1795091 200 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 200 ng IV in combination with pembrolizumab 200 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 200 ng IV will be administered in combination with pembrolizumab 200 mg at Q3W interval.
Drug: GSK1795091 · Drug: Pembrolizumab
Participants will be administered GSK1795091 250 ng IV on Days 1 and 8 followed by once weekly administration of GSK1795091 250 ng IV in combination with pembrolizumab 200 mg administered at Q3W via the IV route until Week 12. From Week 12 onwards, GSK1795091 250 ng IV will be administered in combination with pembrolizumab 200 mg at Q3W interval.
Drug: GSK1795091 · Drug: Pembrolizumab
Participants will be administered GSK1795091 at a dose identified in Part 1 along with GSK3174998 24 mg.
Drug: GSK1795091 · Drug: GSK3174998
Participants will be administered GSK1795091 at a dose identified in Part 1 along with GSK3359609 80 mg.
Drug: GSK1795091 · Drug: GSK3359609
Participants will be administered GSK1795091 at a dose identified in Part 1 along with pembrolizumab 200 mg.
Drug: GSK1795091 · Drug: Pembrolizumab
GSK1795091 will be available as solution for injection
GSK3174998 will be available as lyophilized powder to be reconstituted for infusion.
GSK3359609 will be available as solution for infusion.
Pembrolizumab will be available as solution for infusion or lyophilized powder for reconstitution.
Part 1: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious TEAEs (STEAEs)
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A serious adverse event is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement or associated with liver injury and impaired liver function. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication. All Treated Population consisted of all participants who received at least 1 dose of GSK1795091, GSK3174998, GSK3359609, or pembrolizumab.
Time frame: Up to 27 months
Part 2: Number of Participants With TEAEs and STEAEs
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A serious adverse event is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement or associated with liver injury and impaired liver function. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication.
Time frame: Up to 27 months
Part 1: Number of Participants With Dose-limiting Toxicity (DLT)
An adverse event was considered to be a DLT if it was considered by investigator to be clinically relevant and attributed (definitely, probably or possibly) to study treatment and met one of the criteria: hematologic toxicity-Grade4 neutropenia of \>7 days duration or febrile neutropenia, Grade 4 anemia, Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding as described in Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, non-hematologic toxicity-Grade 4 toxicity, Grade 3 toxicity that does not resolve to \<=Grade 1 or Baseline within 14 days despite optimal supportive care, alanine aminotransferase (ALT) \>=5 times upper limit of normal (ULN), ALT \>=3 times ULN persists for \>=4 weeks, ALT \>=3 times ULN and bilirubin \>=2 times ULN (\>35 percent \[%\] direct bilirubin), ALT \>=3 times ULN and international normalized ratio (INR) \>1.5, ALT \>=3 times ULN associated with symptoms (new or worsening) believed to be related to liver injury or hypersensitivity.
Time frame: 42 days
Part 1: Number of Participants With TEAEs Leading to Discontinuation
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication.
Time frame: Up to 2 years
Part 2: Number of Participants With TEAEs Leading to Discontinuation
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication.
Time frame: Up to 2 years
Part 1: Number of Participants With TEAEs Leading to Dose Reductions or Dose Delays
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication.
Time frame: Up to 2 years
Part 2: Number of Participants With TEAEs Leading to Dose Reductions or Dose Delays
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication.
Time frame: Up to 2 years
Part 1: Number of Participants With Change From Baseline in Hematology Parameters With Respect to the Normal Range
Blood samples were collected for the analysis of following hematology parameters: neutrophils (Neutro), lymphocytes (lympho), monocytes (Mono), eosinophils (Eosino), basophils (Baso), hemoglobin (Hb), hematocrit (Hct), erythrocytes (Erythro), erythrocyte mean corpuscular volume (EMCV), erythrocyte mean corpuscular hemoglobin (EMCH) and platelet count (PC). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Data was categorized as decrease to low (D to L) (value below lower limit of normal range \[LNR\]) and increase to high (I to H) (value above upper LNR). Participants were counted twice if participant had both decreased to low and increased to high within an assessment. Data for worst-case on therapy for categories decrease to low and increase to high is presented.
Time frame: Baseline (Day 1: Pre-dose) and up to 2 years
Part 2: Number of Participants With Change From Baseline in Hematology Parameters With Respect to the Normal Range
Blood samples were planned to be collected for the analysis of following hematology parameters: neutrophils, lymphocytes, monocytes, eosinophils, basophils, hemoglobin, hematocrit, erythrocytes, erythrocyte mean corpuscular volume, erythrocyte mean corpuscular hemoglobin and platelet count.
Time frame: Baseline (Day 1: Pre-dose) and up to 2 years
Part 1: Number of Participants With Change From Baseline in Chemistry Parameters With Respect to the Normal Range
Blood samples were collected for the analysis of following chemistry parameters: urea, creatinine (Cr), glucose (Glu), potassium (Pot), sodium (Sod), calcium (Cal), aspartate aminotransferase (AST), ALT, alkaline phosphatase (ALP), bilirubin (Bil), direct bilirubin (D.Bil), protein, albumin (Alb), C-reactive protein (CRP) and Creatinine Clearance (CrCl). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Data was categorized as decrease to low (value below the lower LNR), and increase to high (value above the upper LNR). Participants were counted twice if the participant had both decreased to low and increased to high within an assessment. Data for worst case on therapy for categories decrease to low and increase to high is presented.
Time frame: Baseline (Day 1: Pre-dose) and up to 2 years
Part 2: Number of Participants With Change From Baseline in Chemistry Parameters With Respect to the Normal Range
Blood samples were planned to be collected for the analysis of following chemistry parameters: urea, creatinine, glucose, potassium, sodium, calcium, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin, direct bilirubin, protein, albumin, C-reactive protein and Creatinine Clearance.
Time frame: Baseline (Day 1: Pre-dose) and up to 2 years
Part 1: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Criteria
Urine samples were collected for the analysis of following urinalysis parameters: glucose (Glu), protein (Pro), occult blood (OB), ketones, potential of hydrogen (pH) and specific gravity (SpGr) by dipstick method. The dipstick test gives results in a semi-quantitative manner. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The reference range is 1.002-1.030. Urine pH is an acid-base measurement. Normal urine has a slightly acid pH (5.0 - 6.0). Data was categorized as decrease to low (value below the lower LNR) and increase to high (value above the upper LNR). Participants were counted twice if the participant had both decreased to low and increased to high within an assessment. Data for worst-case on therapy for categories decrease to low and increase to high is presented.
Time frame: Up to 2 years
Part 2: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Criteria
Urine samples were planned to be collected for the analysis of following urine parameters: glucose, protein, occult blood, ketones, potential of hydrogen and specific gravity by dipstick method.
Time frame: Up to 2 years
Part 1: Number of Participants With Increase From Baseline in Vital Signs According to Markedly Abnormal Criteria
Vital signs including systolic blood pressure (SBP), diastolic BP (DBP), pulse rate (PR) and body temperature (BT) were measured in a semi-supine position after 5 minutes rest for the participants. SBP: Category1 (\>140 and \<161 millimeter of mercury\[mmHg\]), Category 2 (\>=161 and \<181 mmHg), Category3 (\>=181 mmHg); DBP: Category1 (\>90 and \<101 mmHg), Category 2 (\>=101 and \<111 mmHg), Category 3 (\>=111 mmHg); PR: Category 1 (\>101 and \<116 beats per minutes\[bpm\]), Category 2 (\>=116 and \<131 bpm), Category 3 (\>=131 bpm); BT: Category 1 (\>38.0 and \<38.6 degrees Celsius), Category 2 (\>=38.6 and \<39.1 degrees Celsius), Category 3 (\>=39.1 degrees Celsius). Data for any increase in category at worst case on therapy is presented.
Time frame: Up to 2 years
Part 2: Number of Participants With Vital Signs Any Increases From Baseline According to Markedly Abnormal Criteria
Vital signs including SBP, DBP, pulse rate and body temperature were planned to be measured in a semi-supine position after 5 minutes rest for the participants.
Time frame: Up to 2 years
Part 1: Number of Participants With Any Decrease From Baseline in Vital Sign According to Markedly Abnormal Criteria
Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest for the participants. For SBP: a decrease in Category was defined as \<80 mmHg decrease from Baseline; DBP: decrease defined as Category (\<50 mmHg decrease from Baseline); pulse rate: decrease defined as Category (\<45 bpm decrease from Baseline). Data for decrease in category at worst case on therapy is presented.
Time frame: Up to 2 years
Part 2: Number of Participants With Vital Signs Any Decreases From Baseline According to Markedly Abnormal Criteria
Vital signs including SBP, DBP and pulse rate were planned to be measured in a semi-supine position after 5 minutes rest for the participants.
Time frame: Up to 2 years
Part 1: Number of Participants With Any Increase From Baseline in Corrected QT Interval Using Fredericia's Formula (QTcF) According to Markedly Abnormal Criteria
12-lead electrocardiogram (ECG) was obtained at indicated time point using an automated ECG machine that measured QTcF interval. QTc parameters were graded according to National Cancer Institute - CTCAE version 4.0. Grade 1 (\>450 milliseconds \[msec\]), Grade 2 (\>480 msec), Grade 3 (\>500 msec). An increase is defined as an increase in CTCAE grade relative to Baseline grade. Data for any grade increase at worst case on therapy is presented.
Time frame: Up to 2 years
Part 2: Number of Participants With Any QTcF Interval Increases From Baseline According to Markedly Abnormal Criteria
12-lead ECG was planned to be performed to measure QTcF interval.
Time frame: Up to 2 years
Part 1: Objective Response Rate
Objective response rate is defined as the percentage of participants achieving a confirmed best overall response of complete response (CR) or partial response (PR) evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1, where CR=Disappearance of all target lesions. Any pathological lymph nodes must be \<10 millimeters (mm) in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Time frame: Up to 47 months and 13 days
Part 2: Objective Response Rate
Objective response rate is defined as the percentage of participants achieving a confirmed best overall response of CR or PR evaluated using RECIST v 1.1, where CR=Disappearance of all target lesions. Any pathological lymph nodes must be \<10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
Time frame: Up to 47 months and 13 days
Part 1: Disease Control Rate
Disease control rate is defined as the percentage of participants with a confirmed best overall response of CR or PR or at least 12 weeks of stable disease per RECIST v 1.1.
Time frame: Up to 47 months and 13 days
Part 2: Disease Control Rate
Disease control rate is defined as the percentage of participants with a confirmed best overall response of CR or PR or at least 12 weeks of stable disease per RECIST v 1.1.
Time frame: Up to 47 months and 13 days
Part 1: Time to Response
Time to response is defined as the time from the date of first dose to the date of the first documented evidence of response (PR or CR).
Time frame: Up to 47 months and 13 days
Part 2: Time to Response
Time to response is defined as the time from the date of first dose to the date of the first documented evidence of response (PR or CR).
Time frame: Up to 47 months and 13 days
Part 1: Duration of Response
Duration of response is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause among participants who achieve an overall response (that is., a confirmed best overall response of CR or PR) by RECIST v 1.1.
Time frame: Up to 47 months and 13 days
Part 2: Duration of Response
Duration of response is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause among participants who achieve an overall response (that is., a confirmed best overall response of CR or PR) by RECIST v 1.1.
Time frame: Up to 47 months and 13 days
Part 1: Progression-free Survival
Progression-free survival is defined as the interval of time (in months) between the date of first dose to the date of disease progression according to clinical or radiological assessment or death due to any causes, whichever occurs earliest. PFS was determined according to RECIST version 1.1. Progressive disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started.
Time frame: Up to 47 months and 13 days
Part 2: Progression-free Survival
Progression-free survival is defined as the interval of time (in months) between the date of first dose to the date of disease progression according to clinical or radiological assessment or death due to any causes, whichever occurs earliest by RECIST v 1.1. Progressive disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started.
Time frame: Up to 47 months and 13 days
Part 1: Overall Survival
Overall survival is defined as time from the date of first dose of study treatment (whichever investigational drug administered first) to the date of death due to any cause.
Time frame: Up to 47 months and 13 days
Part 2: Overall Survival
Overall survival is defined as time from the date of first dose of study treatment (whichever investigational drug administered first) to the date of death due to any cause.
Time frame: Up to 47 months and 13 days
Part 1a: Plasma Concentration of GSK1795091
Blood samples were collected at indicated time points for the determination of plasma concentration of GSK1795091. Pharmacokinetic (PK) Population consisted of all participants from the All Treated population for whom a PK sample was obtained, analyzed, measurable, and valid.
Time frame: Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Days 78, 162, 246, 414 and 498: 10 minutes post-dose
Part 1b: Plasma Concentration of GSK1795091
Blood samples were collected at indicated time points for the determination of plasma concentration of GSK1795091.
Time frame: Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Day 78: 10 minutes post-dose
Part 1c: Plasma Concentration of GSK1795091
Blood samples were collected at indicated time points for the determination of plasma concentration of GSK1795091.
Time frame: Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Day 78: 10 minutes post-dose
Part 1a: Maximum Plasma Concentration (Cmax) of GSK1795091
Blood samples were collected at indicated time points for the determination of Cmax of GSK1795091.
Time frame: Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Days 78, 162, 246, 414 and 498: 10 minutes post-dose
Part 1b: Cmax of GSK1795091
Blood samples were collected at indicated time points for the determination of Cmax of GSK1795091.
Time frame: Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Day 78: 10 minutes post-dose
Part 1c: Cmax of GSK1795091
Blood samples were collected at indicated time points for the determination of Cmax of GSK1795091.
Time frame: Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Day 78: 10 minutes post-dose
Part 1a: Area Under the Concentration-time Curve Over the Dosing Interval (AUC[0-tau]) GSK1795091
Blood samples were collected at indicated time points for the determination of AUC(0-tau) of GSK1795091.
Time frame: Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Days 78, 162, 246, 414 and 498: 10 minutes post-dose
Part 1b: AUC(0-tau) GSK1795091
Blood samples were collected at indicated time points for the determination of AUC(0-tau) of GSK1795091.
Time frame: Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Day 78: 10 minutes post-dose
Part 1c: AUC(0-tau) GSK1795091
Blood samples were collected at indicated time points for the determination of AUC(0-tau) of GSK1795091.
Time frame: Day 1: Pre-dose, 10 minutes, 2, 4, 6, 24 hours; Day 8: Pre-dose, 10 minutes, 4 hours; Days 15 and 57: Pre-dose, 10 minutes, 4, 24 hours; Day 22: Pre-dose; Day 64: Pre-dose, 10 minutes; Day 78: 10 minutes post-dose
Part 1a: Predose Concentration (Cpre) of GSK1795091
Blood samples were collected at indicated time points for the determination of Cpre of GSK1795091.
Time frame: Days 1, 8, 15, 22, 57, 64, 78, 162, 246, 414 and 498: Pre-dose
Part 1b: Cpre of GSK1795091
Blood samples were collected at indicated time points for the determination of Cpre of GSK1795091.
Time frame: Days 1, 8, 15, 22, 57, 64 and 78: Pre-dose
Part 1c: Cpre of GSK1795091
Blood samples were collected at indicated time points for the determination of Cpre of GSK1795091.
Time frame: Days 1, 8, 15, 22, 57, 64 and 78: Pre-dose
Part 1a: Number of Participants With Present Antidrug Antibody (ADA) Against GSK3174998
Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to GSK3174998. The presence of anti-GSK3174998 antibodies were assessed using a titered approach using validated immunoassays (that is, screening, confirmation, titer, and neutralizing antibody assay).
Time frame: Up to 27 months
Part 1b: Number of Participants With the Present ADA Against GSK3359609
Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to GSK3359609. The presence of anti-GSK3359609 antibodies were assessed using a titered approach using validated immunoassays (that is, screening, confirmation, titer, and neutralizing antibody assay).
Time frame: Up to 27 months
Part 1c: Number of Participants With the Present ADA Against Pembrolizumab
Serum samples were collected at indicated time points for the presence of antibodies that bind to pembrolizumab. The presence of anti-pembrolizumab antibodies were planned to be assessed using a titered approach using validated immunoassays (that is, screening, confirmation, titer, and neutralizing antibody assay).
Time frame: Up to 27 months
Part 2a: Number of Participants With the Present ADA Against GSK3174998
Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to GSK3174998. The presence of anti-GSK3174998 antibodies were were planeed to be assessed using a titered approach using validated immunoassays (that is, screening, confirmation, titer, and neutralizing antibody assay).
Time frame: Up to 2 years
Part 2b: Number of Participants With the Present ADA Against GSK3359609
Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to GSK3359609. The presence of anti-GSK3359609 antibodies were were planeed to be assessed using a titered approach using validated immunoassays (that is, screening, confirmation, titer, and neutralizing antibody assay).
Time frame: Up to 2 years
Part 2c: Number of Participants With the Present ADA Against Pembrolizumab
Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to pembrolizumab. The presence of anti-pembrolizumab antibodies were were planeed to be assessed using a titered approach using validated immunoassays (that is, screening, confirmation, titer, and neutralizing antibody assay).
Time frame: Up to 2 years
Part 1: Number of Participants With TEAEs and STEAEs Until End of the Study
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A serious adverse event is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement or associated with liver injury and impaired liver function. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication.
Time frame: Up to 47 months and 13 days
Part 2: Number of Participants With TEAEs and STEAEs Until End of the Study
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A serious adverse event is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement or associated with liver injury and impaired liver function. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication.
Time frame: Up to 47 months and 13 days
Part 1: Number of Participants With Worst-case Grade Change From Baseline in Hematology Parameters
Blood samples were collected for the analysis of following hematology parameters: neutrophils (Neutro), lymphocytes (lympho) (Low), hemoglobin (Hb) (Low) and platelet count (PC). The laboratory parameters were graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Data for any worst-case on therapy any grade increase has been presented.
Time frame: Up to 2 years
Part 2: Number of Participants With Worst-case Grade Change From Baseline in Hematology Parameters
Blood samples were planned to be collected for the analysis of following hematology parameters: neutrophils (Neutro), lymphocytes (lympho), hemoglobin (Hb) and platelet count (PC).
Time frame: Up to 2 years
Part 1: Number of Participants With Worst-case Grade Change From Baseline in Chemistry Parameters
Blood samples were collected for the analysis of following chemistry parameters: albumin (Hypo), ALP, ALT, AST, bilirubin, calcium (Hyper and Hypo), creatinine, glucose (Hyper and Hypo), potassium (Hyper and Hypo) and sodium (Hyper and Hypo). The laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Data for any worst-case on therapy any grade increase has been presented.
Time frame: Up to 2 years
Part 2: Number of Participants With Worst-case Grade Change From Baseline in Chemistry Parameters
Blood samples were planned to be collected for the analysis of following chemistry parameters: albumin, ALP, ALT, AST, bilirubin, calcium, creatinine, glucose, potassium and sodium.
Time frame: Up to 2 years
This was a non-randomized, open-label study of GSK1795091 administered in combination with immunotherapies in participants with advanced solid tumors.
| Milestone | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab | Part 2a: GSK1795091 + 24 mg GSK3174998 | Part 2b: GSK1795091 + 80 mg GSK3359609 | Part 2c: GSK1795091 + 200 mg Pembrolizumab |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 9 | 6 | 9 | 4 | 2 | 6 | 5 | 0 | 0 | 0 | 7 | 6 | 0 | 0 | 0 | 0 | 0 | 0 |
| Completed | 2 | 1 | 2 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 2 | 3 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 7 | 5 | 7 | 4 | 1 | 6 | 3 | 0 | 0 | 0 | 5 | 3 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Death | 6 | 5 | 4 | 3 | 1 | 4 | 2 | 0 | 0 | 0 | 4 | 3 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Disease progression | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Lost to follow-up | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Reason for discontinuation was not recorded in the case report form | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Withdrew: Investigator discretion | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Milestone | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab | Part 2a: GSK1795091 + 24 mg GSK3174998 | Part 2b: GSK1795091 + 80 mg GSK3359609 | Part 2c: GSK1795091 + 200 mg Pembrolizumab |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A serious adverse event is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement or associated with liver injury and impaired liver function. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication. All Treated Population consisted of all participants who received at least 1 dose of GSK1795091, GSK3174998, GSK3359609, or pembrolizumab.
| Participants | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| TEAEs | 9 | 6 | 9 | 4 | 1 | 6 | 5 | — | — | — | 5 | 6 | — | — | — |
| STEAEs | 1 | 2 | 5 | 1 | 0 | 2 | 2 | — | — | — | 3 | 2 | — | — | — |
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A serious adverse event is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement or associated with liver injury and impaired liver function. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication.
No measurements were reported for this outcome.
An adverse event was considered to be a DLT if it was considered by investigator to be clinically relevant and attributed (definitely, probably or possibly) to study treatment and met one of the criteria: hematologic toxicity-Grade4 neutropenia of \>7 days duration or febrile neutropenia, Grade 4 anemia, Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding as described in Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, non-hematologic toxicity-Grade 4 toxicity, Grade 3 toxicity that does not resolve to \<=Grade 1 or Baseline within 14 days despite optimal supportive care, alanine aminotransferase (ALT) \>=5 times upper limit of normal (ULN), ALT \>=3 times ULN persists for \>=4 weeks, ALT \>=3 times ULN and bilirubin \>=2 times ULN (\>35 percent \[%\] direct bilirubin), ALT \>=3 times ULN and international normalized ratio (INR) \>1.5, ALT \>=3 times ULN associated with symptoms (new or worsening) believed to be related to liver injury or hypersensitivity.
| Participants | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Number of Participants With Dose-limiting Toxicity (DLT) | 0 | 0 | 1 | 0 | 0 | 0 | 0 | — | — | — | 0 | 1 | — | — | — |
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication.
| Participants | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Number of Participants With TEAEs Leading to Discontinuation | 0 | 0 | 1 | 0 | 0 | 0 | 1 | — | — | — | 0 | 1 | — | — | — |
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication.
No measurements were reported for this outcome.
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication.
| Participants | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Number of Participants With TEAEs Leading to Dose Reductions or Dose Delays | 4 | 2 | 1 | 1 | 0 | 2 | 2 | — | — | — | 4 | 2 | — | — | — |
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication.
No measurements were reported for this outcome.
Blood samples were collected for the analysis of following hematology parameters: neutrophils (Neutro), lymphocytes (lympho), monocytes (Mono), eosinophils (Eosino), basophils (Baso), hemoglobin (Hb), hematocrit (Hct), erythrocytes (Erythro), erythrocyte mean corpuscular volume (EMCV), erythrocyte mean corpuscular hemoglobin (EMCH) and platelet count (PC). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Data was categorized as decrease to low (D to L) (value below lower limit of normal range \[LNR\]) and increase to high (I to H) (value above upper LNR). Participants were counted twice if participant had both decreased to low and increased to high within an assessment. Data for worst-case on therapy for categories decrease to low and increase to high is presented.
| Participants | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Neutro, D to L, n=8,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | — | 0 | 1 | — | — | — |
| Neutro, I to H, n=8,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 3 | 0 | 1 | 1 | 0 | 1 | 1 | — | — | — | 3 | 2 | — | — | — |
| Lympho, D to L, n=8,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 4 | 1 | 3 | 0 | 0 | 4 | 0 | — | — | — | 1 | 1 | — | — | — |
| Lympho, I to H, n=8,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | — | 0 | 1 | — | — | — |
| Mono, D to L, n=8,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | — | 0 | 0 | — | — | — |
| Mono, I to H, n=8,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 1 | 1 | 1 | 0 | 0 | 2 | 0 | — | — | — | 0 | 3 | — | — | — |
| Eosino, D to L, n=8,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 0 | 0 | 1 | 1 | 0 | 2 | 0 | — | — | — | 0 | 1 | — | — | — |
| Eosino, I to H, n=8,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 1 | 2 | 1 | 0 | 0 | 2 | 0 | — | — | — | 0 | 2 | — | — | — |
| Baso, D to L, n=8,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | — | 0 | 0 | — | — | — |
| Baso, I to H, n=8,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 | — | — | — | 0 | 0 | — | — | — |
| Hb, D to L, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 2 | 0 | 1 | 1 | 0 | 0 | 1 | — | — | — | 2 | 0 | — | — | — |
| Hb, I to H, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | — | 0 | 0 | — | — | — |
| Hct, D to L, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 2 | 0 | 3 | 1 | 0 | 3 | 1 | — | — | — | 4 | 2 | — | — | — |
| Hct, I to H, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | — | 0 | 0 | — | — | — |
| Erythro, D to L, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 2 | 2 | 2 | 1 | 0 | 1 | 2 | — | — | — | 2 | 2 | — | — | — |
| Erythro, I to H, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | — | 0 | 0 | — | — | — |
| EMCV, D to L, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 2 | 2 | 3 | 0 | 0 | 1 | 1 | — | — | — | 2 | 0 | — | — | — |
| EMCV, I to H, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | — | — | — | 0 | 0 | — | — | — |
| EMCH, D to L, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 3 | 1 | 4 | 1 | 0 | 2 | 2 | — | — | — | 2 | 2 | — | — | — |
| EMCH, I to H, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 2 | 0 | 0 | 0 | 0 | 1 | 0 | — | — | — | 0 | 0 | — | — | — |
| PC, D to L, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | — | 0 | 0 | — | — | — |
| PC, I to H, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | — | — | — | 1 | 3 | — | — | — |
Blood samples were planned to be collected for the analysis of following hematology parameters: neutrophils, lymphocytes, monocytes, eosinophils, basophils, hemoglobin, hematocrit, erythrocytes, erythrocyte mean corpuscular volume, erythrocyte mean corpuscular hemoglobin and platelet count.
No measurements were reported for this outcome.
Blood samples were collected for the analysis of following chemistry parameters: urea, creatinine (Cr), glucose (Glu), potassium (Pot), sodium (Sod), calcium (Cal), aspartate aminotransferase (AST), ALT, alkaline phosphatase (ALP), bilirubin (Bil), direct bilirubin (D.Bil), protein, albumin (Alb), C-reactive protein (CRP) and Creatinine Clearance (CrCl). Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Data was categorized as decrease to low (value below the lower LNR), and increase to high (value above the upper LNR). Participants were counted twice if the participant had both decreased to low and increased to high within an assessment. Data for worst case on therapy for categories decrease to low and increase to high is presented.
| Participants | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Urea, D to L, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 2 | 1 | 1 | 0 | 0 | 0 | 1 | — | — | — | 1 | 1 | — | — | — |
| Urea, I to H, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 3 | 1 | 1 | 1 | 0 | 2 | 0 | — | — | — | 0 | 2 | — | — | — |
| Cr, D to L, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 3 | 0 | 2 | 0 | 0 | 0 | 0 | — | — | — | 4 | 1 | — | — | — |
| Cr, I to H, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 4 | 2 | 0 | 1 | 0 | 1 | 1 | — | — | — | 0 | 0 | — | — | — |
| Glu, D to L, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | — | — | — | 0 | 1 | — | — | — |
| Glu, I to H, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 2 | 0 | 1 | 2 | 1 | 2 | 1 | — | — | — | 1 | 2 | — | — | — |
| Pot, D to L, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | — | 1 | 2 | — | — | — |
| Pot, I to H, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 0 | 0 | 2 | 0 | 0 | 3 | 0 | — | — | — | 0 | 1 | — | — | — |
| Sod, D to L, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 3 | 1 | 2 | 1 | 0 | 2 | 1 | — | — | — | 3 | 2 | — | — | — |
| Sod, I to H, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | — | — | — | 0 | 0 | — | — | — |
| Cal, D to L, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 2 | 1 | 1 | 0 | 1 | 1 | 0 | — | — | — | 2 | 0 | — | — | — |
| Cal, I to H, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 0 | 0 | 3 | 0 | 0 | 0 | 0 | — | — | — | 1 | 1 | — | — | — |
| AST, D to L, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | — | 0 | 0 | — | — | — |
| AST, I to H, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 3 | 2 | 2 | 2 | 0 | 2 | 0 | — | — | — | 2 | 1 | — | — | — |
| ALT, D to L, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | — | 0 | 0 | — | — | — |
| ALT, I to H, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 2 | 1 | 3 | 2 | 0 | 3 | 1 | — | — | — | 0 | 1 | — | — | — |
| ALP, D to L, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | — | 0 | 0 | — | — | — |
| ALP, I to H, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 3 | 1 | 2 | 1 | 0 | 0 | 1 | — | — | — | 2 | 0 | — | — | — |
| Bil, D to L, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | — | — | — | 0 | 1 | — | — | — |
| Bil, I to H, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 3 | 0 | 1 | 0 | 0 | 0 | 1 | — | — | — | 2 | 0 | — | — | — |
| D.Bil, D to L, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | — | 0 | 0 | — | — | — |
| D.Bil, I to H, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 2 | 0 | 2 | 1 | 0 | 0 | 0 | — | — | — | 1 | 0 | — | — | — |
| Protein, D to L, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 3 | 0 | 1 | 2 | 0 | 2 | 0 | — | — | — | 3 | 1 | — | — | — |
| Protein, I to H, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | — | — | — | 0 | 1 | — | — | — |
| Alb, D to L, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 2 | 2 | 2 | 2 | 0 | 1 | 0 | — | — | — | 1 | 2 | — | — | — |
| Alb, I to H, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | — | 0 | 0 | — | — | — |
| CRP, D to L, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | — | 0 | 0 | — | — | — |
| CRP, I to H, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 3 | 1 | 2 | 0 | 1 | 1 | 0 | — | — | — | 1 | 1 | — | — | — |
| CrCl, D to L, n=1,2,3,1,1,4,0,0,0,0,1,2,0,0,0 | 0 | 0 | 2 | 0 | 0 | 0 | — | — | — | — | 0 | 0 | — | — | — |
| CrCl, I to H, n=1,2,3,1,1,4,0,0,0,0,1,2,0,0,0 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | — | — | 0 | 0 | — | — | — |
Blood samples were planned to be collected for the analysis of following chemistry parameters: urea, creatinine, glucose, potassium, sodium, calcium, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, bilirubin, direct bilirubin, protein, albumin, C-reactive protein and Creatinine Clearance.
No measurements were reported for this outcome.
Urine samples were collected for the analysis of following urinalysis parameters: glucose (Glu), protein (Pro), occult blood (OB), ketones, potential of hydrogen (pH) and specific gravity (SpGr) by dipstick method. The dipstick test gives results in a semi-quantitative manner. Urine specific gravity is a measure of the concentration of solutes in the urine and provides information on the kidney's ability to concentrate urine. The reference range is 1.002-1.030. Urine pH is an acid-base measurement. Normal urine has a slightly acid pH (5.0 - 6.0). Data was categorized as decrease to low (value below the lower LNR) and increase to high (value above the upper LNR). Participants were counted twice if the participant had both decreased to low and increased to high within an assessment. Data for worst-case on therapy for categories decrease to low and increase to high is presented.
| Participants | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Glu: D to L, n=9,5,8,1,2,4,2,0,0,0,0,5,0,0,0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | — | — | 0 | — | — | — |
| Glu: I to H, n=9,5,8,1,2,4,2,0,0,0,0,5,0,0,0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | — | — | 0 | — | — | — |
| Pro: D to L, n=9,2,7,1,2,4,0,0,0,0,4,0,0,0,0 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | — | — | 0 | — | — | — | — |
| Pro: I to H, n=9,2,7,1,2,4,0,0,0,0,4,0,0,0,0 | 3 | 0 | 2 | 0 | 0 | 0 | — | — | — | — | 0 | — | — | — | — |
| OB: D to L, n=4,5,8,1,1,4,2,0,0,0,1,4,0,0,0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | — | 0 | 0 | — | — | — |
| OB: I to H, n=4,5,8,1,1,4,2,0,0,0,1,4,0,0,0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | — | — | — | 0 | 0 | — | — | — |
| Ketones: D to L, n=9,5,8,1,2,4,2,0,0,0,0,5,0,0,0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | — | — | 0 | — | — | — |
| Ketones: I to H, n=9,5,8,1,2,4,2,0,0,0,0,5,0,0,0 | 3 | 0 | 3 | 1 | 0 | 1 | 1 | — | — | — | — | 0 | — | — | — |
| pH: D to L, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | — | 0 | 0 | — | — | — |
| pH: I to H, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 0 | 0 | 1 | 1 | 0 | 0 | 0 | — | — | — | 1 | 1 | — | — | — |
| SpGr: D to L, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | — | 0 | 0 | — | — | — |
| SpGr: I to H, n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | — | — | — | 1 | 0 | — | — | — |
Urine samples were planned to be collected for the analysis of following urine parameters: glucose, protein, occult blood, ketones, potential of hydrogen and specific gravity by dipstick method.
No measurements were reported for this outcome.
Vital signs including systolic blood pressure (SBP), diastolic BP (DBP), pulse rate (PR) and body temperature (BT) were measured in a semi-supine position after 5 minutes rest for the participants. SBP: Category1 (\>140 and \<161 millimeter of mercury\[mmHg\]), Category 2 (\>=161 and \<181 mmHg), Category3 (\>=181 mmHg); DBP: Category1 (\>90 and \<101 mmHg), Category 2 (\>=101 and \<111 mmHg), Category 3 (\>=111 mmHg); PR: Category 1 (\>101 and \<116 beats per minutes\[bpm\]), Category 2 (\>=116 and \<131 bpm), Category 3 (\>=131 bpm); BT: Category 1 (\>38.0 and \<38.6 degrees Celsius), Category 2 (\>=38.6 and \<39.1 degrees Celsius), Category 3 (\>=39.1 degrees Celsius). Data for any increase in category at worst case on therapy is presented.
| Participants | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Any increase, SBP | 7 | 3 | 6 | 3 | 1 | 1 | 2 | — | — | — | 2 | 3 | — | — | — |
| Any increase, DBP | 1 | 1 | 3 | 1 | 1 | 1 | 0 | — | — | — | 0 | 3 | — | — | — |
| Any increase, Pulse rate | 2 | 1 | 4 | 1 | 0 | 1 | 2 | — | — | — | 1 | 2 | — | — | — |
| Any increase, Body temperature | 1 | 1 | 2 | 1 | 0 | 0 | 0 | — | — | — | 1 | 0 | — | — | — |
Vital signs including SBP, DBP, pulse rate and body temperature were planned to be measured in a semi-supine position after 5 minutes rest for the participants.
No measurements were reported for this outcome.
Vital signs including SBP, DBP and pulse rate were measured in a semi-supine position after 5 minutes rest for the participants. For SBP: a decrease in Category was defined as \<80 mmHg decrease from Baseline; DBP: decrease defined as Category (\<50 mmHg decrease from Baseline); pulse rate: decrease defined as Category (\<45 bpm decrease from Baseline). Data for decrease in category at worst case on therapy is presented.
| Participants | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Any decrease, SBP | 0 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | — | 0 | 0 | — | — | — |
| Any decrease, DBP | 2 | 1 | 1 | 0 | 0 | 1 | 0 | — | — | — | 0 | 0 | — | — | — |
| Any decrease, Pulse rate | 0 | 0 | 0 | 1 | 0 | 1 | 0 | — | — | — | 0 | 0 | — | — | — |
Vital signs including SBP, DBP and pulse rate were planned to be measured in a semi-supine position after 5 minutes rest for the participants.
No measurements were reported for this outcome.
12-lead electrocardiogram (ECG) was obtained at indicated time point using an automated ECG machine that measured QTcF interval. QTc parameters were graded according to National Cancer Institute - CTCAE version 4.0. Grade 1 (\>450 milliseconds \[msec\]), Grade 2 (\>480 msec), Grade 3 (\>500 msec). An increase is defined as an increase in CTCAE grade relative to Baseline grade. Data for any grade increase at worst case on therapy is presented.
| Participants | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Number of Participants With Any Increase From Baseline in Corrected QT Interval Using Fredericia's Formula (QTcF) According to Markedly Abnormal Criteria | 2 | 1 | 2 | 0 | 0 | 3 | 0 | — | — | — | 1 | 1 | — | — | — |
12-lead ECG was planned to be performed to measure QTcF interval.
No measurements were reported for this outcome.
Objective response rate is defined as the percentage of participants achieving a confirmed best overall response of complete response (CR) or partial response (PR) evaluated using Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1, where CR=Disappearance of all target lesions. Any pathological lymph nodes must be \<10 millimeters (mm) in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
| Percentage of participants | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Objective Response Rate | 11.1 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | — | — | — | 0.0 | 33.3 | — | — | — |
Objective response rate is defined as the percentage of participants achieving a confirmed best overall response of CR or PR evaluated using RECIST v 1.1, where CR=Disappearance of all target lesions. Any pathological lymph nodes must be \<10 mm in the short axis. PR=At least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters.
No measurements were reported for this outcome.
Disease control rate is defined as the percentage of participants with a confirmed best overall response of CR or PR or at least 12 weeks of stable disease per RECIST v 1.1.
| Percentage of participants | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Disease Control Rate | 44.4 | 33.3 | 33.3 | 25.0 | 0.0 | 16.7 | 20.0 | — | — | — | 14.3 | 33.3 | — | — | — |
Disease control rate is defined as the percentage of participants with a confirmed best overall response of CR or PR or at least 12 weeks of stable disease per RECIST v 1.1.
No measurements were reported for this outcome.
Time to response is defined as the time from the date of first dose to the date of the first documented evidence of response (PR or CR).
| Months | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Time to Response | 5.6 (5.6 to 5.6) | — | — | — | — | — | — | — | — | — | — | 2.0 (1.6 to 2.4) | — | — | — |
Time to response is defined as the time from the date of first dose to the date of the first documented evidence of response (PR or CR).
No measurements were reported for this outcome.
Duration of response is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause among participants who achieve an overall response (that is., a confirmed best overall response of CR or PR) by RECIST v 1.1.
| Months | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Duration of Response | 13.73 (13.73 to 13.73) | — | — | — | — | — | — | — | — | — | — | NA (16.82 to NA) | — | — | — |
Duration of response is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause among participants who achieve an overall response (that is., a confirmed best overall response of CR or PR) by RECIST v 1.1.
No measurements were reported for this outcome.
Progression-free survival is defined as the interval of time (in months) between the date of first dose to the date of disease progression according to clinical or radiological assessment or death due to any causes, whichever occurs earliest. PFS was determined according to RECIST version 1.1. Progressive disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started.
| Months | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Progression-free Survival | 2.79 (2.64 to 5.13) | 3.29 (2.46 to 3.61) | 2.60 (2.00 to 7.46) | 2.25 (1.45 to 3.96) | NA (NA to NA) | 2.28 (1.91 to 2.79) | 1.41 (1.15 to 2.46) | — | — | — | 2.22 (1.91 to 2.43) | 2.37 (2.33 to 19.22) | — | — | — |
Progression-free survival is defined as the interval of time (in months) between the date of first dose to the date of disease progression according to clinical or radiological assessment or death due to any causes, whichever occurs earliest by RECIST v 1.1. Progressive disease is defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started.
No measurements were reported for this outcome.
Overall survival is defined as time from the date of first dose of study treatment (whichever investigational drug administered first) to the date of death due to any cause.
| Months | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1: Overall Survival | 9.03 (6.29 to NA) | 7.75 (3.61 to 9.03) | 16.69 (8.03 to NA) | 6.72 (3.20 to 9.86) | 11.14 (11.14 to 11.14) | 4.48 (3.15 to 8.38) | 2.89 (2.37 to NA) | — | — | — | 3.91 (2.66 to NA) | NA (6.08 to NA) | — | — | — |
Overall survival is defined as time from the date of first dose of study treatment (whichever investigational drug administered first) to the date of death due to any cause.
No measurements were reported for this outcome.
Blood samples were collected at indicated time points for the determination of plasma concentration of GSK1795091. Pharmacokinetic (PK) Population consisted of all participants from the All Treated population for whom a PK sample was obtained, analyzed, measurable, and valid.
| Picogram per milliliter | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 |
|---|---|---|---|---|---|
| Day 1: Pre-dose, n=9,5,9,4,2 | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 0.00) |
| Day 1: 10 minutes, n=7,5,9,4,2 | 3.960 (0.00 to 5.80) | 4.920 (4.00 to 11.90) | 28.800 (5.59 to 53.40) | 56.330 (43.60 to 68.05) | 82.175 (64.97 to 99.38) |
| Day 1: 2 hours, n=8,5,9,4,2 | 1.580 (0.00 to 4.02) | 4.090 (2.49 to 5.92) | 29.200 (2.87 to 48.80) | 57.195 (35.97 to 63.79) | 62.285 (57.57 to 67.00) |
| Day 1: 4 hours, n=8,5,9,4,2 | 3.680 (0.00 to 4.41) | 3.680 (2.29 to 5.67) | 27.300 (2.11 to 46.90) | 47.315 (33.66 to 61.52) | 60.945 (56.43 to 65.46) |
| Day 1: 6 hours, n=8,3,9,4,1 | 0.000 (0.00 to 2.82) | 3.470 (2.50 to 4.66) | 25.700 (0.00 to 40.20) | 46.040 (32.61 to 64.30) | 57.180 (NA to NA) |
| Day 1: 24 hours, n=8,5,9,4,2 | 0.000 (0.00 to 2.68) | 2.190 (0.00 to 3.70) | 15.800 (0.00 to 29.30) | 35.265 (27.09 to 44.10) | 39.120 (32.73 to 45.51) |
| Day 8: Pre-dose, n=8,5,8,3,1 | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 5.25) | 4.590 (3.52 to 10.05) | 4.160 (NA to NA) |
| Day 8: 10 minutes, n=9,5,8,3,1 | 4.300 (0.00 to 10.20) | 6.160 (5.01 to 8.89) | 30.850 (2.28 to 60.54) | 71.910 (55.71 to 74.13) | 89.510 (NA to NA) |
| Day 8: 4 hours, n=8,5,7,2,1 | 3.190 (0.00 to 6.80) | 3.790 (0.00 to 5.03) | 16.000 (0.00 to 37.40) | 61.830 (54.29 to 69.37) | 65.030 (NA to NA) |
| Day 15: Pre-dose, n=9,3,9,2,0 | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 5.99) | 4.975 (4.73 to 5.22) | — |
| Day 15: 10 minutes, n=8,4,8,3,0 | 5.255 (3.40 to 14.50) | 5.120 (4.35 to 8.96) | 35.625 (7.96 to 53.40) | 57.570 (46.52 to 76.81) | — |
| Day 15: 4 hours, n=9,3,6,3,0 | 2.830 (0.00 to 7.24) | 4.210 (2.75 to 5.02) | 25.675 (3.15 to 51.30) | 50.950 (43.71 to 62.64) | — |
| Day 15: 24 hours, n=9,3,8,3,0 | 0.000 (0.00 to 3.43) | 3.050 (2.36 to 3.43) | 18.970 (0.00 to 34.10) | 41.770 (36.87 to 50.89) | — |
| Day 22: Pre-dose, n=9,3,7,3,0 | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 5.60) | 4.450 (4.21 to 11.90) | — |
| Day 57: Pre-dose, n=6,3,6,0,0 | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 0.00) | 1.215 (0.00 to 24.77) | — | — |
| Day 57: 10 minutes, n=4,3,4,1,0 | 6.400 (3.03 to 8.94) | 7.470 (6.08 to 18.20) | 32.600 (6.87 to 41.31) | 60.090 (NA to NA) | — |
| Day 57: 4 hours, n=4,3,6,1,0 | 3.855 (0.00 to 6.13) | 3.530 (3.36 to 16.30) | 13.735 (2.45 to 34.34) | 55.980 (NA to NA) | — |
| Day 57: 24 hours, n=6,4,6,2,0 | 0.000 (0.00 to 5.55) | 2.665 (2.41 to 11.60) | 16.595 (0.00 to 26.60) | 51.390 (45.48 to 57.30) | — |
| Day 64: Pre-dose, n=4,4,4,1,0 | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 0.00) | 3.040 (0.00 to 46.20) | 15.300 (NA to NA) | — |
| Day 64: 10 minutes, n=5,4,3,2,0 | 3.340 (0.00 to 4.18) | 7.055 (4.95 to 20.60) | 26.700 (12.00 to 42.10) | 75.045 (74.38 to 75.71) | — |
| Day 78: 10 minutes, n=5,3,4,2,0 | 3.980 (2.10 to 10.50) | 10.100 (6.80 to 24.80) | 22.700 (5.48 to 45.20) | 72.215 (67.82 to 76.61) | — |
| Day 162: 10 minutes, n=1,0,0,0,0 | 3.450 (NA to NA) | — | — | — | — |
| Day 246: 10 minutes, n=1,0,0,0,0 | 37.200 (NA to NA) | — | — | — | — |
| Day 414: 10 minutes, n=1,0,0,0,0 | 18.600 (NA to NA) | — | — | — | — |
| Day 498: 10 minutes, n=1,0,0,0,0 | 0.000 (NA to NA) | — | — | — | — |
Blood samples were collected at indicated time points for the determination of plasma concentration of GSK1795091.
| Picogram per milliliter | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 |
|---|---|---|---|---|---|
| Day 1: Pre-dose, n=6,5,0,0,0 | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 0.00) | — | — | — |
| Day 1: 10 minutes, n=6,5,0,0,0 | 12.870 (0.00 to 15.80) | 32.300 (27.10 to 40.10) | — | — | — |
| Day 1: 2 hours, n=6,5,0,0,0 | 14.100 (0.00 to 28.80) | 29.770 (25.60 to 37.10) | — | — | — |
| Day 1: 4 hours, n=6,5,0,0,0 | 13.000 (0.00 to 14.40) | 25.330 (23.30 to 32.40) | — | — | — |
| Day 1: 6 hours, n=6,4,0,0,0 | 12.065 (0.00 to 13.40) | 23.690 (21.10 to 30.28) | — | — | — |
| Day 1: 24 hours, n=6,4,0,0,0 | 7.680 (0.00 to 9.17) | 19.650 (17.88 to 22.30) | — | — | — |
| Day 8: Pre-dose, n=5,4,0,0,0 | 0.000 (0.00 to 0.00) | 2.215 (0.00 to 2.74) | — | — | — |
| Day 8: 10 minutes, n=5,4,0,0,0 | 15.280 (2.97 to 17.28) | 29.550 (29.30 to 35.64) | — | — | — |
| Day 8: 4 hours, n=5,4,0,0,0 | 11.460 (0.00 to 15.94) | 23.850 (18.97 to 30.49) | — | — | — |
| Day 15: Pre-dose, n=4,3,0,0,0 | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 4.44) | — | — | — |
| Day 15: 10 minutes, n=4,4,0,0,0 | 16.000 (3.62 to 19.05) | 27.645 (25.70 to 49.04) | — | — | — |
| Day 15: 4 hours, n=4,4,0,0,0 | 10.145 (2.70 to 15.20) | 24.100 (17.82 to 34.97) | — | — | — |
| Day 15: 24 hours, n=5,2,0,0,0 | 6.890 (0.00 to 12.48) | 14.735 (10.87 to 18.60) | — | — | — |
| Day 22: Pre-dose, n=5,2,0,0,0 | 0.000 (0.00 to 2.45) | 1.015 (0.00 to 2.03) | — | — | — |
| Day 57: Pre-dose, n=3,1,0,0,0 | 0.000 (0.00 to 3.33) | 2.300 (NA to NA) | — | — | — |
| Day 57: 10 minutes, n=3,2,0,0,0 | 14.620 (12.20 to 17.86) | 28.155 (25.98 to 30.33) | — | — | — |
| Day 57: 4 hours, n=1,1,0,0,0 | 12.140 (NA to NA) | 25.510 (NA to NA) | — | — | — |
| Day 57: 24 hours, n=3,2,0,0,0 | 8.250 (6.59 to 11.44) | 17.530 (16.44 to 18.62) | — | — | — |
| Day 64: Pre-dose, n=1,2,0,0,0 | 0.000 (NA to NA) | 1.875 (0.00 to 3.75) | — | — | — |
| Day 64: 10 minutes, n=2,2,0,0,0 | 6.910 (0.00 to 13.82) | 34.345 (32.14 to 36.55) | — | — | — |
| Day 78: 10 minutes, n=2,2,0,0,0 | 6.980 (2.48 to 11.48) | 34.875 (32.02 to 37.73) | — | — | — |
Blood samples were collected at indicated time points for the determination of plasma concentration of GSK1795091.
| Picogram per milliliter | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|
| Day 1: Pre-dose, n=7,6,0,0,0 | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 0.00) | — | — | — |
| Day 1: 10 minutes, n=7,6,0,0,0 | 13.600 (0.00 to 14.00) | 27.965 (13.20 to 38.64) | — | — | — |
| Day 1: 2 hours, n=6,6,0,0,0 | 11.475 (0.00 to 12.77) | 28.775 (10.50 to 56.63) | — | — | — |
| Day 1: 4 hours, n=7,6,0,0,0 | 9.890 (0.00 to 12.20) | 25.970 (10.10 to 32.63) | — | — | — |
| Day 1: 6 hours, n=7,6,0,0,0 | 9.460 (0.00 to 12.54) | 24.415 (8.83 to 33.69) | — | — | — |
| Day 1: 24 hours, n=7,6,0,0,0 | 8.370 (0.00 to 10.14) | 15.825 (6.31 to 24.03) | — | — | — |
| Day 8: Pre-dose, n=6,5,0,0,0 | 0.000 (0.00 to 0.00) | 2.060 (0.00 to 2.51) | — | — | — |
| Day 8: 10 minutes, n=7,5,0,0,0 | 12.810 (0.00 to 16.00) | 24.260 (14.80 to 35.30) | — | — | — |
| Day 8: 4 hours, n=6,5,0,0,0 | 9.420 (2.56 to 13.68) | 23.390 (12.30 to 27.70) | — | — | — |
| Day 15: Pre-dose, n=3,4,0,0,0 | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 3.26) | — | — | — |
| Day 15: 10 minutes, n=7,6,0,0,0 | 9.200 (0.00 to 14.70) | 28.015 (12.60 to 54.93) | — | — | — |
| Day 15: 4 hours, n=7,4,0,0,0 | 7.070 (0.00 to 11.60) | 17.825 (6.81 to 26.60) | — | — | — |
| Day 15: 24 hours, n=7,5,0,0,0 | 4.580 (0.00 to 8.42) | 11.230 (5.53 to 19.80) | — | — | — |
| Day 22: Pre-dose, n=4,3,0,0,0 | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 3.49) | — | — | — |
| Day 57: Pre-dose, n=2,1,0,0,0 | 0.000 (0.00 to 0.00) | 0.000 (NA to NA) | — | — | — |
| Day 57: 10 minutes, n=2,1,0,0,0 | 14.665 (12.80 to 16.53) | 23.840 (NA to NA) | — | — | — |
| Day 57: 4 hours, n=2,0,0,0,0 | 10.515 (10.13 to 10.90) | — | — | — | — |
| Day 57: 24 hours, n=2,2,0,0,0 | 7.460 (6.72 to 8.20) | 9.780 (4.87 to 14.69) | — | — | — |
| Day 64: Pre-dose, n=2,1,0,0,0 | 0.000 (0.00 to 0.00) | 0.000 (NA to NA) | — | — | — |
| Day 64: 10 minutes, n=3,1,0,0,0 | 13.570 (11.50 to 14.00) | 31.680 (NA to NA) | — | — | — |
| Day 78: 10 minutes, n=2,0,0,0,0 | 15.455 (14.71 to 16.20) | — | — | — | — |
Blood samples were collected at indicated time points for the determination of Cmax of GSK1795091.
| Picogram per milliliter | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 |
|---|---|---|---|---|---|
| Day 1, n=7,5,9,4,2 | 4.180 (3.16 to 5.80) | 4.920 (4.00 to 11.9) | 29.20 (5.59 to 53.4) | 59.95 (43.6 to 68.1) | 82.18 (65.0 to 99.4) |
| Day 8, n=8,5,8,3,1 | 4.720 (2.49 to 10.2) | 6.160 (5.01 to 8.89) | 30.85 (2.28 to 60.5) | 71.91 (55.7 to 74.1) | 89.51 (NA to NA) |
| Day 15, n=9,4,8,3,0 | 5.110 (2.47 to 14.5) | 5.120 (4.35 to 8.96) | 35.63 (7.96 to 53.4) | 57.57 (46.5 to 76.8) | — |
| Day 57, n=4,3,4,1,0 | 6.400 (3.03 to 8.94) | 7.470 (6.08 to 18.2) | 32.60 (6.87 to 41.3) | 60.09 (NA to NA) | — |
| Day 64, n=5,4,3,2,0 | 3.340 (0.00 to 4.18) | 7.055 (4.95 to 20.6) | 26.70 (12.0 to 42.1) | 75.05 (74.4 to 75.7) | — |
| Day 78, n=5,3,4,2,0 | 3.980 (2.10 to 10.5) | 10.10 (6.80 to 24.8) | 22.70 (5.48 to 45.2) | 72.22 (67.8 to 76.6) | — |
| Day 162, n=1,0,0,0,0 | 3.450 (NA to NA) | — | — | — | — |
| Day 246, n=1,0,0,0,0 | 37.20 (NA to NA) | — | — | — | — |
| Day 414, n=1,0,0,0,0 | 18.60 (NA to NA) | — | — | — | — |
| Day 498, n=1,0,0,0,0 | 0.000 (NA to NA) | — | — | — | — |
Blood samples were collected at indicated time points for the determination of Cmax of GSK1795091.
| Picogram per milliliter | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 |
|---|---|---|---|---|---|
| Day 1, n=6,5,0,0,0 | 14.95 (2.23 to 28.8) | 32.30 (27.1 to 40.1) | — | — | — |
| Day 8, n=5,4,0,0,0 | 15.28 (2.97 to 17.3) | 29.55 (29.3 to 35.6) | — | — | — |
| Day 15, n=4,4,0,0,0 | 16.00 (3.62 to 19.1) | 27.80 (25.7 to 49.0) | — | — | — |
| Day 57, n=3,2,0,0,0 | 14.62 (13.2 to 17.9) | 28.16 (26.0 to 30.3) | — | — | — |
| Day 64, n=2,2,0,0,0 | 6.910 (0.00 to 13.8) | 34.35 (32.1 to 36.6) | — | — | — |
| Day 78, n=2,2,0,0,0 | 6.980 (2.48 to 11.5) | 34.88 (32.0 to 37.7) | — | — | — |
Blood samples were collected at indicated time points for the determination of Cmax of GSK1795091.
| Picogram per milliliter | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|
| Day 1, n=6,6,0,0,0 | 13.75 (6.04 to 14.0) | 30.56 (13.2 to 56.6) | — | — | — |
| Day 8, n=6,5,0,0,0 | 13.53 (5.44 to 16.0) | 25.35 (14.8 to 35.3) | — | — | — |
| Day 15, n=6,6,0,0,0 | 10.19 (4.60 to 14.7) | 28.02 (12.6 to 54.9) | — | — | — |
| Day 57, n=2,1,0,0,0 | 14.67 (12.8 to 16.5) | 23.84 (NA to NA) | — | — | — |
| Day 64, n=3,1,0,0,0 | 13.57 (11.5 to 14.0) | 31.68 (NA to NA) | — | — | — |
| Day 78, n=2,0,0,0,0 | 15.46 (14.7 to 16.2) | — | — | — | — |
Blood samples were collected at indicated time points for the determination of AUC(0-tau) of GSK1795091.
| Hours*picogram per milliliter | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 |
|---|---|---|---|---|---|
| Day 1, n=5,5,8,3,1 | 48.08 (35.0 to 276) | 227.6 (39.0 to 383) | 1804 (41.0 to 2540) | 3615 (2390 to 4300) | 4166 (NA to NA) |
| Day 15, n=2,2,6,3,0 | 256.7 (191 to 322) | 318.3 (294 to 343) | 1907 (273 to 3000) | 3479 (3020 to 4900) | — |
| Day 57, n=0,3,2,1,0 | — | 267.9 (247 to 1140) | 2027 (1410 to 2640) | 3515 (NA to NA) | — |
Blood samples were collected at indicated time points for the determination of AUC(0-tau) of GSK1795091.
| Hours*picogram per milliliter | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 |
|---|---|---|---|---|---|
| Day 1, n=4,4,0,0,0 | 819.1 (721 to 899) | 1840 (1560 to 2120) | — | — | — |
| Day 15, n=3,2,0,0,0 | 661.9 (632 to 916) | 1453 (1100 to 1800) | — | — | — |
| Day 57, n=1,2,0,0,0 | 845.2 (NA to NA) | 1757 (1740 to 1780) | — | — | — |
Blood samples were collected at indicated time points for the determination of AUC(0-tau) of GSK1795091.
| Hours*picogram per milliliter | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|
| Day 1, n=4,5,0,0,0 | 851.7 (208 to 990) | 1611 (645 to 1710) | — | — | — |
| Day 15, n=3,2,0,0,0 | 566.9 (460 to 815) | 1189 (540 to 1840) | — | — | — |
| Day 57, n=2,1,0,0,0 | 778.0 (750 to 805) | 1640 (NA to NA) | — | — | — |
Blood samples were collected at indicated time points for the determination of Cpre of GSK1795091.
| Picogram per milliliter | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 |
|---|---|---|---|---|---|
| Day 8, n=8,5,8,3,1 | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 5.25) | 4.590 (3.52 to 10.1) | 4.160 (NA to NA) |
| Day 15, n=9,3,8,2,0 | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 5.99) | 4.975 (4.73 to 5.22) | — |
| Day 22, n=9,3,7,3,0 | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 5.60) | 4.450 (4.21 to 11.9) | — |
| Day 57, n=4,3,4,0,0 | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 0.00) | 1.215 (0.00 to 6.02) | — | — |
| Day 64, n=4,4,4,1,0 | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 0.00) | 3.040 (0.00 to 46.2) | 15.30 (NA to NA) | — |
Blood samples were collected at indicated time points for the determination of Cpre of GSK1795091.
| Picogram per milliliter | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 |
|---|---|---|---|---|---|
| Day 8, n=5,4,0,0,0 | 0.000 (0.00 to 0.00) | 2.215 (0.00 to 2.74) | — | — | — |
| Day 15, n=4,3,0,0,0 | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 4.44) | — | — | — |
| Day 22, n=5,2,0,0,0 | 0.000 (0.00 to 2.45) | 1.015 (0.00 to 2.03) | — | — | — |
| Day 57, n=3,1,0,0,0 | 0.000 (0.00 to 3.33) | 2.300 (NA to NA) | — | — | — |
| Day 64, n=1,2,0,0,0 | 0.000 (NA to NA) | 1.875 (0.00 to 3.75) | — | — | — |
Blood samples were collected at indicated time points for the determination of Cpre of GSK1795091.
| Picogram per milliliter | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|
| Day 8, n=5,5,0,0,0 | 0.000 (0.00 to 0.00) | 2.060 (0.00 to 2.51) | — | — | — |
| Day 15, n=3,4,0,0,0 | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 3.26) | — | — | — |
| Day 22, n=3,3,0,0,0 | 0.000 (0.00 to 0.00) | 0.000 (0.00 to 3.49) | — | — | — |
| Day 57, n=2,1,0,0,0 | 0.000 (0.00 to 0.00) | 0.000 (NA to NA) | — | — | — |
| Day 64, n=2,1,0,0,0 | 0.000 (0.00 to 0.00) | 0.000 (NA to NA) | — | — | — |
Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to GSK3174998. The presence of anti-GSK3174998 antibodies were assessed using a titered approach using validated immunoassays (that is, screening, confirmation, titer, and neutralizing antibody assay).
| Participants | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 |
|---|---|---|---|---|---|
| Part 1a: Number of Participants With Present Antidrug Antibody (ADA) Against GSK3174998 | 5 | 0 | 2 | 1 | 0 |
Serum samples were collected at indicated time points and tested for the presence of antibodies that bind to GSK3359609. The presence of anti-GSK3359609 antibodies were assessed using a titered approach using validated immunoassays (that is, screening, confirmation, titer, and neutralizing antibody assay).
| Participants | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 |
|---|---|---|---|---|---|
| Part 1b: Number of Participants With the Present ADA Against GSK3359609 | 0 | 1 | — | — | — |
Serum samples were collected at indicated time points for the presence of antibodies that bind to pembrolizumab. The presence of anti-pembrolizumab antibodies were planned to be assessed using a titered approach using validated immunoassays (that is, screening, confirmation, titer, and neutralizing antibody assay).
| Participants | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|
| Part 1c: Number of Participants With the Present ADA Against Pembrolizumab | NA | NA | — | — | — |
Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to GSK3174998. The presence of anti-GSK3174998 antibodies were were planeed to be assessed using a titered approach using validated immunoassays (that is, screening, confirmation, titer, and neutralizing antibody assay).
No measurements were reported for this outcome.
Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to GSK3359609. The presence of anti-GSK3359609 antibodies were were planeed to be assessed using a titered approach using validated immunoassays (that is, screening, confirmation, titer, and neutralizing antibody assay).
No measurements were reported for this outcome.
Serum samples were planned to be collected at indicated time points and tested for the presence of antibodies that bind to pembrolizumab. The presence of anti-pembrolizumab antibodies were were planeed to be assessed using a titered approach using validated immunoassays (that is, screening, confirmation, titer, and neutralizing antibody assay).
No measurements were reported for this outcome.
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A serious adverse event is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement or associated with liver injury and impaired liver function. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication.
| Participants | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| TEAEs | 9 | 6 | 9 | 4 | 1 | 6 | 5 | — | — | — | 5 | 6 | — | — | — |
| STEAEs | 1 | 2 | 5 | 1 | 0 | 2 | 2 | — | — | — | 3 | 2 | — | — | — |
An adverse event is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A serious adverse event is defined as any untoward medical occurrence that, at any dose; results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situation according to medical or scientific judgement or associated with liver injury and impaired liver function. TEAEs are defined as adverse events that started or worsened in severity on or after the first dose of study medication.
No measurements were reported for this outcome.
Blood samples were collected for the analysis of following hematology parameters: neutrophils (Neutro), lymphocytes (lympho) (Low), hemoglobin (Hb) (Low) and platelet count (PC). The laboratory parameters were graded according to National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Data for any worst-case on therapy any grade increase has been presented.
| Participants | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Neutro: n=8,6,9,4,2,6,4,0,0,0,6,6,0,0,0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | — | — | — | 0 | 2 | — | — | — |
| Lympho (Low): n=8,6,9,4,2,6,4,0,0,0,6,6,0,0,0 | 7 | 3 | 4 | 0 | 0 | 5 | 0 | — | — | — | 2 | 3 | — | — | — |
| Hb (Low): n=9,6,9,4,2,6,4,0,0,0,7,6,0,0,0 | 6 | 4 | 3 | 2 | 0 | 2 | 3 | — | — | — | 2 | 3 | — | — | — |
| PC: n=9,6,9,4,2,6,4,0,0,0,7,6,0,0,0 | 2 | 1 | 0 | 0 | 0 | 0 | 0 | — | — | — | 0 | 1 | — | — | — |
Blood samples were planned to be collected for the analysis of following hematology parameters: neutrophils (Neutro), lymphocytes (lympho), hemoglobin (Hb) and platelet count (PC).
No measurements were reported for this outcome.
Blood samples were collected for the analysis of following chemistry parameters: albumin (Hypo), ALP, ALT, AST, bilirubin, calcium (Hyper and Hypo), creatinine, glucose (Hyper and Hypo), potassium (Hyper and Hypo) and sodium (Hyper and Hypo). The laboratory parameters were graded according to NCI-CTCAE version 4.0. Grade 1: mild; Grade 2: moderate; Grade 3: severe or medically significant; Grade 4: life-threatening consequences. Higher grade indicates greater severity and an increase in CTCAE grade was defined relative to the Baseline grade. Baseline was defined as the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Data for any worst-case on therapy any grade increase has been presented.
| Participants | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Albumin (Hypo): n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 4 | 2 | 2 | 2 | 0 | 2 | 2 | — | — | — | 1 | 3 | — | — | — |
| ALP: n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 5 | 1 | 4 | 1 | 0 | 3 | 2 | — | — | — | 2 | 1 | — | — | — |
| ALT: n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 2 | 2 | 4 | 2 | 0 | 3 | 2 | — | — | — | 1 | 2 | — | — | — |
| AST: n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 3 | 2 | 4 | 2 | 0 | 3 | 2 | — | — | — | 2 | 2 | — | — | — |
| Bilirubin: n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 3 | 0 | 2 | 0 | 0 | 1 | 1 | — | — | — | 2 | 1 | — | — | — |
| Calcium (Hyper): n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 0 | 0 | 4 | 0 | 0 | 1 | 0 | — | — | — | 1 | 2 | — | — | — |
| Calcium (Hypo): n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 2 | 1 | 1 | 0 | 1 | 1 | 0 | — | — | — | 2 | 0 | — | — | — |
| Creatinine: n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 4 | 3 | 1 | 2 | 0 | 2 | 1 | — | — | — | 0 | 1 | — | — | — |
| Glucose (Hyper): n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 7 | 0 | 4 | 2 | 2 | 3 | 1 | — | — | — | 1 | 3 | — | — | — |
| Glucose (Hypo): n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 0 | 0 | 0 | 1 | 0 | 1 | 1 | — | — | — | 0 | 1 | — | — | — |
| Potassium (Hyper): n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 1 | 0 | 3 | 0 | 0 | 3 | 0 | — | — | — | 0 | 2 | — | — | — |
| Potassium (Hypo): n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 4 | 0 | 0 | 0 | 1 | 1 | 0 | — | — | — | 2 | 2 | — | — | — |
| Sodium (Hyper): n=9,6,9,4,2,0,0,0,0,0,7,6,0,0,0 | 0 | 0 | 1 | 0 | 0 | — | — | — | — | — | 0 | 1 | — | — | — |
| Sodium (Hypo): n=9,6,9,4,2,6,5,0,0,0,7,6,0,0,0 | 3 | 3 | 3 | 1 | 1 | 4 | 1 | — | — | — | 4 | 3 | — | — | — |
Blood samples were planned to be collected for the analysis of following chemistry parameters: albumin, ALP, ALT, AST, bilirubin, calcium, creatinine, glucose, potassium and sodium.
No measurements were reported for this outcome.
Collected over All-cause mortality, non-serious TEAEs and STEAEs were collected up to 47 months and 13 days in Part 1. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | 6/9 (66.7%) | 1/9 (11.1%) | 9/9 (100%) |
| Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | 5/6 (83.3%) | 2/6 (33.3%) | 6/6 (100%) |
| Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | 4/9 (44.4%) | 5/9 (55.6%) | 9/9 (100%) |
| Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | 4/4 (100%) | 1/4 (25%) | 4/4 (100%) |
| Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | 1/2 (50%) | 0/2 (0%) | 1/2 (50%) |
| Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | 5/6 (83.3%) | 2/6 (33.3%) | 6/6 (100%) |
| Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | 3/5 (60%) | 2/5 (40%) | 5/5 (100%) |
| Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | 4/7 (57.1%) | 3/7 (42.9%) | 5/7 (71.4%) |
| Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | 3/6 (50%) | 2/6 (33.3%) | 5/6 (83.3%) |
| Event | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|---|---|---|---|
| HaematuriaRenal and urinary disorders | 0/9 | 0/6 | 0/9 | 1/4 | 0/2 | 0/6 | 0/5 | 0/7 | 0/6 |
| UrosepsisInfections and infestations | 0/9 | 0/6 | 0/9 | 1/4 | 0/2 | 0/6 | 0/5 | 0/7 | 0/6 |
| Gastrointestinal disorderGastrointestinal disorders | 0/9 | 0/6 | 0/9 | 0/4 | 0/2 | 0/6 | 1/5 | 0/7 | 0/6 |
| Hepatobiliary diseaseHepatobiliary disorders | 0/9 | 0/6 | 0/9 | 0/4 | 0/2 | 0/6 | 1/5 | 0/7 | 0/6 |
| Blood bilirubin increasedInvestigations | 0/9 | 0/6 | 0/9 | 0/4 | 0/2 | 0/6 | 1/5 | 1/7 | 0/6 |
| ConstipationGastrointestinal disorders | 0/9 | 1/6 | 0/9 | 0/4 | 0/2 | 0/6 | 0/5 | 0/7 | 0/6 |
| BronchitisInfections and infestations | 0/9 | 0/6 | 0/9 | 0/4 | 0/2 | 0/6 | 0/5 | 0/7 | 1/6 |
| Peritonitis bacterialInfections and infestations | 0/9 | 0/6 | 0/9 | 0/4 | 0/2 | 1/6 | 0/5 | 0/7 | 0/6 |
| SepsisInfections and infestations | 0/9 | 0/6 | 0/9 | 0/4 | 0/2 | 1/6 | 0/5 | 1/7 | 0/6 |
| HyponatraemiaMetabolism and nutrition disorders | 0/9 | 0/6 | 0/9 | 0/4 | 0/2 | 1/6 | 0/5 | 0/7 | 0/6 |
| Event | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab |
|---|---|---|---|---|---|---|---|---|---|
| ChillsGeneral disorders | 5/9 | 6/6 | 3/9 | 2/4 | 0/2 | 2/6 | 2/5 | 0/7 | 2/6 |
| NauseaGastrointestinal disorders | 6/9 | 2/6 | 2/9 | 0/4 | 0/2 | 3/6 | 2/5 | 3/7 | 2/6 |
| FatigueGeneral disorders | 6/9 | 2/6 | 6/9 | 0/4 | 0/2 | 2/6 | 0/5 | 1/7 | 3/6 |
| VomitingGastrointestinal disorders | 5/9 | 1/6 | 3/9 | 0/4 | 0/2 | 0/6 | 0/5 | 2/7 | 1/6 |
| AnaemiaBlood and lymphatic system disorders | 3/9 | 2/6 | 2/9 | 1/4 | 0/2 | 3/6 | 2/5 | 1/7 | 1/6 |
| DiarrhoeaGastrointestinal disorders | 0/9 | 2/6 | 2/9 | 0/4 | 1/2 | 0/6 | 1/5 | 0/7 | 1/6 |
| DehydrationMetabolism and nutrition disorders | 0/9 | 3/6 | 0/9 | 0/4 | 0/2 | 1/6 | 0/5 | 0/7 | 0/6 |
| Weight decreasedInvestigations | 4/9 | 1/6 | 0/9 | 0/4 | 0/2 | 0/6 | 1/5 | 0/7 | 1/6 |
| Blood alkaline phosphatase increasedInvestigations | 0/9 | 0/6 | 1/9 | 0/4 | 0/2 | 0/6 | 1/5 | 3/7 | 0/6 |
| PruritusSkin and subcutaneous tissue disorders | 0/9 | 1/6 | 1/9 | 0/4 | 0/2 | 0/6 | 0/5 | 3/7 | 1/6 |
Part 1b and Part 1c (GSK1795091 150ng, 200ng, 250ng arms) were not initiated as GSK1795091 was no longer supplied due to a manufacturing issue. Hence, no participants were enrolled in Part 1b and Part 1c (GSK1795091 150ng, 200ng, 250ng arms); Part 2 was not initiated.
| Age, Customized(Participants) | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab | Part 2a: GSK1795091 + 24 mg GSK3174998 | Part 2b: GSK1795091 + 80 mg GSK3359609 | Part 2c: GSK1795091 + 200 mg Pembrolizumab | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 19 - 64 years | 8 | 3 | 7 | 3 | 0 | 5 | 4 | 0 | 0 | 0 | 4 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 37 |
| >=65 years | 1 | 3 | 2 | 1 | 2 | 1 | 1 | 0 | 0 | 0 | 3 | 3 | 0 | 0 | 0 | 0 | 0 | 0 | 17 |
| Sex: Female, Male(Participants) | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab | Part 2a: GSK1795091 + 24 mg GSK3174998 | Part 2b: GSK1795091 + 80 mg GSK3359609 | Part 2c: GSK1795091 + 200 mg Pembrolizumab | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Female | 4 | 3 | 3 | 2 | 0 | 4 | 3 | 0 | 0 | 0 | 5 | 4 | 0 | 0 | 0 | 0 | 0 | 0 | 28 |
| Male | 5 | 3 | 6 | 2 | 2 | 2 | 2 | 0 | 0 | 0 | 2 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 26 |
| Race/Ethnicity, Customized(Participants) | Part 1a: 50ng GSK1795091 + 24mg GSK3174998 | Part 1a: 100ng GSK1795091 + 24mg GSK3174998 | Part 1a: 150ng GSK1795091 + 24mg GSK3174998 | Part 1a: 200ng GSK1795091 + 24mg GSK3174998 | Part 1a: 250ng GSK1795091 + 24mg GSK3174998 | Part 1b: 50ng GSK1795091 + 80mg GSK3359609 | Part 1b: 100ng GSK1795091 + 80mg GSK3359609 | Part 1b: 150ng GSK1795091 + 80mg GSK3359609 | Part 1b: 200ng GSK1795091 + 80mg GSK3359609 | Part 1b: 250ng GSK1795091 + 80mg GSK3359609 | Part 1c: 50ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 100ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 150ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 200ng GSK1795091 + 200mg Pembrolizumab | Part 1c: 250ng GSK1795091 + 200mg Pembrolizumab | Part 2a: GSK1795091 + 24 mg GSK3174998 | Part 2b: GSK1795091 + 80 mg GSK3359609 | Part 2c: GSK1795091 + 200 mg Pembrolizumab | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Asian - East Asian Heritage | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Asian - Central/South Asian Heritage | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| White - Arabic/North African Heritage | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| White - White/Caucasian/European Heritage | 6 | 6 | 7 | 4 | 2 | 5 | 5 | 0 | 0 | 0 | 6 | 5 | 0 | 0 | 0 | 0 | 0 | 0 | 46 |
| Unknown | 2 | 0 | 2 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — GSK will assess requests from qualified researchers for anonymized individual patient-level data (IPD) and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About_GSK_Patient_Level_Data_Sharing_Final_13July2023.pdf
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report
Time frame: Anonymized IPD is made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
Access criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
Data sharing details ↗ · www.gsk-studyregister.com
Ran from Mar 2018 to primary completion in Jul 2020, 27 months.
Results were first posted in Jul 2021, 1 year after primary completion.
Of 677 industry-sponsored phase 1 interventional studies under Neoplasms, half reached primary completion within 38 months of starting (the median), counting those still running; a quarter within 22 and three quarters within 61. This study's 27 months is below that.
Counting every sponsor, half of 904 studies reached it within 40 months; a quarter within 23 and three quarters within 64.
Neoplasms covers many different conditions, not one, so the studies compared here vary widely. Read these figures as a rough guide.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Sep 2024. You cannot join it, but the record below documents what was studied.
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