A Phase 2 interventional study of Niraparib and Pembrolizumab in Neoplasms, sponsored by Tesaro, Inc.. Completed at 16 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2023-10-16.
Sponsored by Tesaro, Inc. (part of GlaxoSmithKline) · Phase 2, Interventional, and Treatment
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This is a multicenter, open-label, phase 2 study to evaluate the efficacy and safety of niraparib alone and in combination with PD-1 inhibitors in participants with locally advanced and metastatic non-small cell lung cancer (NSCLC). The study will consist of 2 stages. In stage 1, participants from Cohorts 1 and 2 will receive niraparib plus PD-1 inhibitor; pembrolizumab and participants from Cohort 3 will receive niraparib alone. In Stage 2, participants from Cohorts 1A and 2A will receive niraparib plus the PD-1 inhibitor, TSR-042 (Dostarlimab).
10,824 studies on the registry are indexed under Neoplasms; 2,325 are open to participants now.
This study's enrollment of 53 is below the median of 60 across 7,706 interventional studies indexed under Neoplasms.
Browse Neoplasms studies →Tesaro, Inc. is the lead sponsor of 33 studies on the registry; none are open to participants now.
Of its 12 completed or terminated interventional studies of FDA-regulated products, 12 (100%) have results posted.
First submitted before Tesaro, Inc. became part of GlaxoSmithKline.
Counted across the registry records on this site, refreshed daily.
General Inclusion Criteria:
Adequate organ function, defined as:
Female participant meets the following criteria:
a) Female participant (of ) is not breastfeeding, has a negative serum pregnancy test within 72 hours prior to taking study drug, and agrees to abstain from activities that could result in pregnancy from enrollment through 180 days after the last dose of study treatment or is of nonchildbearing potential; or b) Female participant is of nonchildbearing potential, other than medical reasons, defined as follows: i) >=45 years of age and has not had menses for > 1 year. ii) Amenorrheic for \< 2 years without a hysterectomy and oophorectomy and a follicle-stimulating hormone (FSH) value in the range upon screening evaluation.
iii) Post hysterectomy, bilateral oophorectomy, or tubal ligation. Documented hysterectomy or oophorectomy must be confirmed with medical records of the actual procedure or confirmed by an ultrasound. Tubal ligation must be confirmed with medical records of the actual procedure, otherwise the participant must be willing to use 2 highly effective methods throughout the study, starting with the screening visit through 180 days after the last dose of study therapy.
Cohort Specific Inclusion Criteria:
Exclusion Criteria for Cohorts 1, 1A , 2 and 2A:
Exclusion criteria for Cohort 3:
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.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
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 number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.
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.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
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.
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.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
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.
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.
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.
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
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.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
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 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.
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.
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
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.
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.
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.
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.
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.
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.
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.
Absolute neutrophil count (ANC)
The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.
It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (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.
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.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
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.
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.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
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.
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.
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.
Adjuvant and neoadjuvant
Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.
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.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
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.
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.
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.
Leptomeningeal disease
Cancer that has spread to the leptomeninges, the thin layers covering the brain and spinal cord, and the fluid between them. It is not the same as brain metastases.
Criteria often treat it separately, and many studies leave it out even where treated brain metastases are allowed.
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.
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.
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.
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.
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 with locally advanced and metastatic NSCLC (all histologies) with no prior systemic chemotherapy or PD-1/programmed death-ligand 1 (PD-L1) inhibitor treatment and whose tumors have high PD-L1 expression (tumor proportion score \[TPS\]: \>= 50 percent \[%\]) will receive combination of niraparib and a PD-1 inhibitor; pembrolizumab.
Drug: Niraparib · Biological: Pembrolizumab
Participants with locally advanced and metastatic NSCLC (all histologies) with no prior systemic chemotherapy or PD-1/PD-L1 inhibitor treatment and whose tumors have PD-L1 expression (TPS: 1% to 49%) will receive combination of niraparib and a PD-1 inhibitor; pembrolizumab.
Drug: Niraparib · Biological: Pembrolizumab
Participants with locally advanced and metastatic squamous NSCLC who have been previously treated with both platinum and either PD-1 or PD-L1 inhibitor will receive single agent niraparib.
Drug: Niraparib
Participants with locally advanced and metastatic NSCLC (all histologies) with no prior systemic chemotherapy or PD-1/PD-L1 inhibitor treatment and whose tumors have high PD-L1 expression (TPS: \>= 50%) will receive combination of niraparib and a PD-1 inhibitor; TSR-042 (Dostarlimab).
Drug: Niraparib · Biological: TSR-042 (Dostarlimab)
Participants with locally advanced and metastatic NSCLC (all histologies) with no prior systemic chemotherapy or PD-1/PD-L1 inhibitor treatment and whose tumors have PD-L1 expression (TPS: 1% to 49%) will receive combination of niraparib and a PD-1 inhibitor; TSR-042 (Dostarlimab).
Drug: Niraparib · Biological: TSR-042 (Dostarlimab)
Niraparib is an orally available, potent, highly selective poly adenosine diphosphate- ribose (poly ADP-ribose) polymerase-1 (PARP-1) and PARP-2 inhibitor. It will be available as 100 milligrams (mg) capsules and will be administered as 2 X 100 mg capsules (200 mg per day) orally once daily (QD).
Pembrolizumab is a potent and highly selective humanized monoclonal antibody (mAb) of the immunoglobulin G-4 (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands (PD-L1 and PD-L2). It will be available as 50 mg lyophilized powder single-use vials or 100 mg/4 milliliters (mL) (25 mg/mL) solution in a single-dose vial. It will be administered at a dose of 200 mg intravenous (IV) using a 30-minute IV infusion
TSR-042 (Dostarlimab) is a humanized mAb of the IgG4/kappa isotype that binds with high affinity to PD-1, resulting in inhibition of binding to PD-L1 and PD-L2. It will be administered at a dose of 500 mg for every 3 weeks (Q3W) for first 4 cycles followed by 1000 mg for every 6 weeks (Q6W) for all subsequent cycles using a 30-minute IV infusion. TSR-042 (dostarlimab) will be supplied as a solution of 160 mg (20 mg/mL) or 500 mg (50 mg/mL) in a single-dose vial.
Stage 1: Cohort 1: Objective Response Rate (ORR)
ORR is the percentage of participants with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) in the analysis population 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 percent (%) decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. Tumor assessment was done by the Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Data has been presented for participants with NSCLC whose tumors have high PD-L1 expression (TPS\>=50%). Confidence interval was calculated using binomial exact method.
Time frame: Up to a maximum of 29 months
Stage 1: Cohort 2: Objective Response Rate
ORR is the percentage of participants with a confirmed BOR of CR or PR in the analysis population 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. Tumor assessment was done by the Investigator per RECIST v1.1. Data has been presented for participants with NSCLC having PD-L1 expression in tumors (TPS: 1 to 49%). Confidence interval was calculated using binomial exact method.
Time frame: Up to a maximum of 17 months
Stage 1: Cohort 3: Objective Response Rate
ORR is the percentage of participants with a confirmed BOR of CR or PR in the analysis population 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. Tumor assessment was done by the Investigator per RECIST v1.1. Data is presented for participants with locally advanced and metastatic squamous NSCLC. Confidence interval was calculated using binomial exact method.
Time frame: Up to a maximum of 6 months
Stage 2: Cohort 1A and Cohort 2A: Objective Response Rate
ORR is the percentage of participants with a confirmed BOR of CR or PR in the analysis population 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. Tumor assessment was done by the Investigator per RECIST v1.1. Confidence interval was calculated using binomial exact method.
Time frame: Up to a maximum of 17 months
Stage 1: Cohort 1: Number of Participants With Non-serious Adverse Events (Non-SAEs) and Serious Adverse Events (SAEs)
An adverse event (AE) is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not Serious Adverse Events were considered as Non-Serious adverse events
Time frame: Up to a maximum of 45 months
Stage 1: Cohort 2: Number of Participants With Non-SAEs and SAEs
An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not Serious Adverse Events were considered as Non-Serious adverse events
Time frame: Up to a maximum of 17 months
Stage 1: Cohort 3: Number of Participants With Non-SAEs and SAEs
An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not Serious Adverse Events were considered as Non-Serious adverse events
Time frame: Up to a maximum of 6 months
Stage 2: Cohorts 1A and 2A: Number of Participants With Non-SAEs and SAEs
An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not Serious Adverse Events were considered as Non-Serious adverse events.
Time frame: Up to a maximum of 29 months
Stage 1: Cohort 1: Number of Participants Discontinuing the Study Due to AEs
An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. Number of participants discontinuing the study due to AEs have been summarized.
Time frame: Up to a maximum of 45 months
Stage 1: Cohort 2: Number of Participants Discontinuing the Study Due to AEs
An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. Number of participants discontinuing the study due to AEs have been summarized.
Time frame: Up to a maximum of 17 months
Stage 1: Cohort 3: Number of Participants Discontinuing the Study Due to AEs
An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. Number of participants discontinuing the study due to AEs have been summarized.
Time frame: Up to a maximum of 6 months
Stage 2: Cohorts 1A and 2A: Number of Participants Discontinuing the Study Due to AEs
An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. Number of participants discontinuing the study due to AEs have been summarized.
Time frame: Up to maximum 29 months
Stage 1: Cohort 1: Duration of Response
Duration of Response was defined as the time from first documented CR or PR until the subsequently documented disease progression by RECIST v1.1 or death, whichever occurs earlier; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be \<10 millimeter (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 a maximum of 45 months
Stage 1: Cohort 2: Duration of Response
Duration of Response was defined as the time from first documented CR or PR until the subsequently documented disease progression by RECIST v1.1 or death, whichever occurs earlier; 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 a maximum of 17 months
Stage 1 : Cohort 3: Duration of Response
Duration of Response was defined as the time from first documented CR or PR until the subsequently documented disease progression by RECIST v1.1 or death, whichever occurs earlier; 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 a maximum of 6 months
Stage 2: Cohorts 1A and 2A: Duration of Response
Duration of Response was defined as the time from first documented CR or PR until the subsequently documented disease progression by RECIST v1.1 or death, whichever occurs earlier; 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 a maximum of 29 months
Stage 1 : Cohort 1: Disease Control Rate
Disease Control Rate was defined as the percentage of participants with a best overall response of CR, PR or SD per RECIST v1.1; 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. Confidence interval was calculated using binomial exact method.
Time frame: Up to a maximum of 45 months
Stage 1 : Cohort 2: Disease Control Rate
Disease Control Rate was defined as the percentage of participants with a best overall response of CR, PR or SD per RECIST v1.1; 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. Confidence interval was calculated using binomial exact method.
Time frame: Up to a maximum of 17 months
Stage 1 : Cohort 3: Disease Control Rate
Disease Control Rate was defined as the percentage of participants with a best overall response of CR, PR or SD per RECIST v1.1; 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. Confidence interval was calculated using binomial exact method.
Time frame: Up to a maximum of 6 months
Stage 2: Cohorts 1A and 2A: Disease Control Rate
Disease Control Rate was defined as the percentage of participants with a best overall response of CR, PR or SD per RECIST v1.1; 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. Confidence interval was calculated using binomial exact method.
Time frame: Up to a maximum of 29 months
Stage 1 : Cohort 1: Progression-free Survival
Progression-free survival was defined as the time from the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. Progression was defined using RECIST v1.1 as a 20% increase in the sum of the diameter of target lesions or unequivocal progression of existing non-target lesions or the appearance of one or more new lesions.
Time frame: Up to a maximum of 45 months
Stage 1 : Cohort 2: Progression-free Survival
Progression-free survival was defined as the time from the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. Progression was defined using RECIST v1.1 as a 20% increase in the sum of the diameter of target lesions or unequivocal progression of existing non-target lesions or the appearance of one or more new lesions.
Time frame: Up to a maximum of 17 months
Stage 1 : Cohort 3: Progression-free Survival
Progression-free survival was defined as the time from the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. Progression was defined using RECIST v1.1 as a 20% increase in the sum of the diameter of target lesions or unequivocal progression of existing non-target lesions or the appearance of one or more new lesions.
Time frame: Up to a maximum of 6 months
Stage 2: Cohorts 1A and 2A: Progression-free Survival
Progression-free survival was defined as the time from the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. Progression was defined using RECIST v1.1 as a 20% increase in the sum of the diameter of target lesions or unequivocal progression of existing non-target lesions or the appearance of one or more new lesions.
Time frame: Up to a maximum of 29 months
Stage 1: Cohort 1: Plasma Concentration of Niraparib Following Combination Therapy of Niraparib and Pembrolizumab
Blood samples were collected at indicated time points.
Time frame: Cycle 1 Day 1(Pre-dose and 30 Minutes, 1 Hour, 2 Hours, 4 Hours, 8 Hours, 96 Hours, 168 Hours Post-dose); Cycles 2, 4, 8 (Pre-dose and 4 Hours Post-dose) (each cycle of 21 days)
Stage 1: Cohort 2: Plasma Concentration of Niraparib Following Combination Therapy of Niraparib and Pembrolizumab
Blood samples were collected at indicated time points.
Time frame: Cycle 1 Day 1 (Pre-dose and 30 Minutes, 1, 2, 4, 8, 24, 168, 336 Hours Post-dose), Cycles 2, 8 (Pre-dose and 4 Hours Post-dose), Cycle 4 (Pre-dose and 30 Minutes, 1, 2, 4, 8, 24, 96, 168, 336 Hours Post-dose) (each cycle of 21 days)
Stage 1: Cohort 3: Plasma Concentration of Niraparib Following Niraparib Monotherapy
Blood samples were collected at indicated time points.
Time frame: Cycle 1 Day 1 (Pre-dose and 4 Hours Post-dose), Cycles 2, 4 and 8 (Pre-dose and 4 Hours Post-dose) (each cycle of 21 days)
Stage 2: Cohorts 1A and 2A: Plasma Concentration of Niraparib Following Combination Therapy of Niraparib and TSR-042 (Dostarlimab)
Blood samples were collected at indicated time points.
Time frame: Cycle 1 Day 1 (Pre-dose and 4 Hours Post-dose), Cycles 2, 4 and 9 (Pre-dose and 4 Hours Post-dose) (each cycle of 21 days)
Stage 1: Cohort 1: Overall Survival (OS)
Overall survival was defined as the time from date of first dose to the date of death due to any cause.
Time frame: Up to a maximum of 45 months
Stage 1: Cohort 2: Overall Survival
Overall survival was defined as the time from date of first dose to the date of death due to any cause.
Time frame: Up to a maximum of 17 months
Stage 1: Cohort 3: Overall Survival
Overall survival was defined as the time from date of first dose to the date of death due to any cause.
Time frame: Up to a maximum of 6 months
Stage 2: Cohorts 1A and 2A: Overall Survival
Overall survival was defined as the time from date of first dose to the date of death due to any cause.
Time frame: Up to a maximum of 29 months
This study consisted of two stages; Stage 1 (Cohorts 1, 2, 3) and Stage 2 (Cohorts 1A, 2A).
| Milestone | Stage 1 (Cohort 1): Niraparib + Pembrolizumab | Stage 1 (Cohort 2): Niraparib + Pembrolizumab | Stage 1 (Cohort 3): Niraparib | Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab) | Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab) |
|---|---|---|---|---|---|
| Started | 17 | 21 | 3 | 0 | 0 |
| Completed | 0 | 0 | 0 | 0 | 0 |
| Not completed | 17 | 21 | 3 | 0 | 0 |
| Withdrew: Withdrawal by subject | 3 | 3 | 2 | 0 | 0 |
| Withdrew: Death | 11 | 16 | 1 | 0 | 0 |
| Withdrew: Lost to follow-up | 0 | 1 | 0 | 0 | 0 |
| Withdrew: Sponsor decision | 3 | 1 | 0 | 0 | 0 |
| Milestone | Stage 1 (Cohort 1): Niraparib + Pembrolizumab | Stage 1 (Cohort 2): Niraparib + Pembrolizumab | Stage 1 (Cohort 3): Niraparib | Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab) | Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab) |
|---|---|---|---|---|---|
| Started | 0 | 0 | 0 | 12 | 0 |
| Completed | 0 | 0 | 0 | 0 | 0 |
| Not completed | 0 | 0 | 0 | 12 | 0 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 3 | 0 |
| Withdrew: Death | 0 | 0 | 0 | 6 | 0 |
| Withdrew: Sponsor decision | 0 | 0 | 0 | 3 | 0 |
ORR is the percentage of participants with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) in the analysis population 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 percent (%) decrease in the sum of the diameters of target lesions, taking as a reference, the Baseline sum of the diameters. Tumor assessment was done by the Investigator per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1. Data has been presented for participants with NSCLC whose tumors have high PD-L1 expression (TPS\>=50%). Confidence interval was calculated using binomial exact method.
| Percentage of participants | Stage 1 (Cohort 1): Niraparib + Pembrolizumab |
|---|---|
| Stage 1: Cohort 1: Objective Response Rate (ORR) | 56.3 (29.9 to 80.2) |
ORR is the percentage of participants with a confirmed BOR of CR or PR in the analysis population 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. Tumor assessment was done by the Investigator per RECIST v1.1. Data has been presented for participants with NSCLC having PD-L1 expression in tumors (TPS: 1 to 49%). Confidence interval was calculated using binomial exact method.
| Percentage of participants | Stage 1 (Cohort 2): Niraparib + Pembrolizumab |
|---|---|
| Stage 1: Cohort 2: Objective Response Rate | 20.0 (5.7 to 43.7) |
ORR is the percentage of participants with a confirmed BOR of CR or PR in the analysis population 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. Tumor assessment was done by the Investigator per RECIST v1.1. Data is presented for participants with locally advanced and metastatic squamous NSCLC. Confidence interval was calculated using binomial exact method.
| Percentage of participants | Stage 1 (Cohort 3): Niraparib |
|---|---|
| Stage 1: Cohort 3: Objective Response Rate | 0 (0.0 to 84.2) |
ORR is the percentage of participants with a confirmed BOR of CR or PR in the analysis population 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. Tumor assessment was done by the Investigator per RECIST v1.1. Confidence interval was calculated using binomial exact method.
| Percentage of participants | Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab) | Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab) |
|---|---|---|
| Stage 2: Cohort 1A and Cohort 2A: Objective Response Rate | 9.1 (0.2 to 41.3) | — |
An adverse event (AE) is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not Serious Adverse Events were considered as Non-Serious adverse events
| Participants | Stage 1 (Cohort 1): Niraparib + Pembrolizumab |
|---|---|
| Any SAE | 11 |
| Any non-SAE | 17 |
An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not Serious Adverse Events were considered as Non-Serious adverse events
| Participants | Stage 1 (Cohort 2): Niraparib + Pembrolizumab |
|---|---|
| Any SAE | 14 |
| Any non-SAE | 20 |
An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not Serious Adverse Events were considered as Non-Serious adverse events
| Participants | Stage 1 (Cohort 3): Niraparib |
|---|---|
| Any SAE | 1 |
| Any non-SAE | 3 |
An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. A SAE is defined as any untoward medical occurrence that, at any dose that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, is an important medical event(s) as per medical and scientific judgment. Adverse events which were not Serious Adverse Events were considered as Non-Serious adverse events.
| Participants | Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab) | Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab) |
|---|---|---|
| Any SAE | 7 | — |
| Any non-SAE | 12 | — |
An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. Number of participants discontinuing the study due to AEs have been summarized.
| Participants | Stage 1 (Cohort 1): Niraparib + Pembrolizumab |
|---|---|
| Stage 1: Cohort 1: Number of Participants Discontinuing the Study Due to AEs | 10 |
An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. Number of participants discontinuing the study due to AEs have been summarized.
| Participants | Stage 1 (Cohort 2): Niraparib + Pembrolizumab |
|---|---|
| Stage 1: Cohort 2: Number of Participants Discontinuing the Study Due to AEs | 9 |
An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. Number of participants discontinuing the study due to AEs have been summarized.
| Participants | Stage 1 (Cohort 3): Niraparib |
|---|---|
| Stage 1: Cohort 3: Number of Participants Discontinuing the Study Due to AEs | 1 |
An AE is any untoward medical occurrence that occurs in a participant or clinical investigation participant administered a pharmaceutical product, and which does not necessarily have to have a causal relationship with this treatment. Number of participants discontinuing the study due to AEs have been summarized.
| Participants | Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab) | Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab) |
|---|---|---|
| Stage 2: Cohorts 1A and 2A: Number of Participants Discontinuing the Study Due to AEs | 2 | — |
Duration of Response was defined as the time from first documented CR or PR until the subsequently documented disease progression by RECIST v1.1 or death, whichever occurs earlier; where CR=Disappearance of all target lesions. Any pathological lymph nodes must be \<10 millimeter (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.
| Months | Stage 1 (Cohort 1): Niraparib + Pembrolizumab |
|---|---|
| Stage 1: Cohort 1: Duration of Response | 22.8 (10.1 to NA) |
Duration of Response was defined as the time from first documented CR or PR until the subsequently documented disease progression by RECIST v1.1 or death, whichever occurs earlier; 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.
| Months | Stage 1 (Cohort 2): Niraparib + Pembrolizumab |
|---|---|
| Stage 1: Cohort 2: Duration of Response | 9.4 (5.2 to 13.8) |
Duration of Response was defined as the time from first documented CR or PR until the subsequently documented disease progression by RECIST v1.1 or death, whichever occurs earlier; 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.
Duration of Response was defined as the time from first documented CR or PR until the subsequently documented disease progression by RECIST v1.1 or death, whichever occurs earlier; 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.
| Months | Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab) | Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab) |
|---|---|---|
| Stage 2: Cohorts 1A and 2A: Duration of Response | 21.5 (NA to NA) | — |
Disease Control Rate was defined as the percentage of participants with a best overall response of CR, PR or SD per RECIST v1.1; 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. Confidence interval was calculated using binomial exact method.
| Percentage of participants | Stage 1 (Cohort 1): Niraparib + Pembrolizumab |
|---|---|
| Stage 1 : Cohort 1: Disease Control Rate | 87.5 (61.7 to 98.4) |
Disease Control Rate was defined as the percentage of participants with a best overall response of CR, PR or SD per RECIST v1.1; 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. Confidence interval was calculated using binomial exact method.
| Percentage of participants | Stage 1 (Cohort 2): Niraparib + Pembrolizumab |
|---|---|
| Stage 1 : Cohort 2: Disease Control Rate | 70.0 (45.7 to 88.1) |
Disease Control Rate was defined as the percentage of participants with a best overall response of CR, PR or SD per RECIST v1.1; 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. Confidence interval was calculated using binomial exact method.
| Percentage of participants | Stage 1 (Cohort 3): Niraparib |
|---|---|
| Stage 1 : Cohort 3: Disease Control Rate | 50.0 (1.3 to 98.7) |
Disease Control Rate was defined as the percentage of participants with a best overall response of CR, PR or SD per RECIST v1.1; 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. Confidence interval was calculated using binomial exact method.
| Percentage of participants | Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab) | Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab) |
|---|---|---|
| Stage 2: Cohorts 1A and 2A: Disease Control Rate | 54.5 (23.4 to 83.3) | — |
Progression-free survival was defined as the time from the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. Progression was defined using RECIST v1.1 as a 20% increase in the sum of the diameter of target lesions or unequivocal progression of existing non-target lesions or the appearance of one or more new lesions.
| Months | Stage 1 (Cohort 1): Niraparib + Pembrolizumab |
|---|---|
| Stage 1 : Cohort 1: Progression-free Survival | 8.4 (3.9 to 36.2) |
Progression-free survival was defined as the time from the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. Progression was defined using RECIST v1.1 as a 20% increase in the sum of the diameter of target lesions or unequivocal progression of existing non-target lesions or the appearance of one or more new lesions.
| Months | Stage 1 (Cohort 2): Niraparib + Pembrolizumab |
|---|---|
| Stage 1 : Cohort 2: Progression-free Survival | 4.2 (2.0 to 6.2) |
Progression-free survival was defined as the time from the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. Progression was defined using RECIST v1.1 as a 20% increase in the sum of the diameter of target lesions or unequivocal progression of existing non-target lesions or the appearance of one or more new lesions.
| Months | Stage 1 (Cohort 3): Niraparib |
|---|---|
| Stage 1 : Cohort 3: Progression-free Survival | 4.0 (1.3 to 6.6) |
Progression-free survival was defined as the time from the date of first dose to the date of disease progression or death due to any cause, whichever occurs earlier. Progression was defined using RECIST v1.1 as a 20% increase in the sum of the diameter of target lesions or unequivocal progression of existing non-target lesions or the appearance of one or more new lesions.
| Months | Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab) | Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab) |
|---|---|---|
| Stage 2: Cohorts 1A and 2A: Progression-free Survival | 4.4 (2.0 to NA) | — |
Blood samples were collected at indicated time points.
| Nanograms per milliliter | Stage 1 (Cohort 1): Niraparib + Pembrolizumab |
|---|---|
| Cycle 1 Day 1; Pre-dose | 28.4 ± 115 |
| Cycle 1 Day 1; 30 Minutes Post-dose | 201 ± NA |
| Cycle 1 Day 1; 1 Hour Post-dose | 500 ± NA |
| Cycle 1 Day 1; 2 Hours Post-dose | 733 ± NA |
| Cycle 1 Day 1; 4 Hours Post-dose | 335 ± 233 |
| Cycle 1 Day 1; 8 Hours Post-dose | 353 ± NA |
| Cycle 1 Day 1; 96 Hours Post-dose | 1400 ± NA |
| Cycle 1 Day 1; 168 Hours Post-dose | 1440 ± NA |
| Cycle 2; Pre-dose | 360 ± 383 |
| Cycle 2; 4 Hours Post-dose | 959 ± 506 |
| Cycle 4; Pre-dose | 600 ± 505 |
| Cycle 4; 4 Hours Post-dose | 794 ± 597 |
| Cycle 8; Pre-dose | 460 ± 543 |
| Cycle 8; 4 Hours Post-dose | 727 ± 824 |
Blood samples were collected at indicated time points.
| Nanograms per milliliter | Stage 1 (Cohort 2): Niraparib + Pembrolizumab |
|---|---|
| Cycle 1 Day 1; Pre-dose | NA ± NA |
| Cycle 1 Day 1; 30 Minutes Post-dose | 24.5 ± 42.4 |
| Cycle 1 Day 1; 1 Hour Post-dose | 189 ± 302 |
| Cycle 1 Day 1; 2 Hours Post-dose | 264 ± 251 |
| Cycle 1 Day 1; 4 Hours Post-dose | 345 ± 188 |
| Cycle 1 Day 1; 8 Hours Post-dose | 238 ± NA |
| Cycle 1 Day 1; 24 Hours Post-dose | 318 ± NA |
| Cycle 1 Day 1; 168 Hours Post-dose | 759 ± NA |
| Cycle 1 Day 1; 336 Hours Post-dose | 808 ± NA |
| Cycle 2; Pre-dose | 767 ± 362 |
| Cycle 2; 4 Hours Post-dose | 1170 ± 473 |
| Cycle 4; Pre-dose | 805 ± 588 |
| Cycle 4; 30 Minutes Post-dose | 841 ± NA |
| Cycle 4; 1 Hour Post-dose | 1260 ± NA |
| Cycle 4; 2 Hours Post-dose | 1290 ± NA |
| Cycle 4; 4 Hours Post-dose | 1040 ± 668 |
| Cycle 4; 8 Hours, Post-dose | 978 ± NA |
| Cycle 4; 24 Hours Post-dose | 660 ± NA |
| Cycle 4; 96 Hours | 773 ± NA |
| Cycle 4; 168 Hours | 767 ± NA |
| Cycle 4; 336 Hours | 924 ± NA |
| Cycle 8; Pre-dose | 342 ± 123 |
| Cycle 8; 4 Hours post-dose | 602 ± 290 |
Blood samples were collected at indicated time points.
| Nanograms per milliliter | Stage 1 (Cohort 3): Niraparib |
|---|---|
| Cycle 1 Day 1; Pre-dose | NA ± NA |
| Cycle 1 Day 1; 4 Hours Post-dose | 279 ± NA |
| Cycle 2; Pre-dose | 469 ± NA |
| Cycle 2; 4 Hours Post-dose | 717 ± NA |
| Cycle 4; Pre-dose | 615 ± NA |
| Cycle 4; 4 Hours Post-dose | 871 ± NA |
| Cycle 8; Pre-dose | 478 ± NA |
| Cycle 8; 4 Hours Post-dose | 913 ± NA |
Blood samples were collected at indicated time points.
| Nanograms per milliliter | Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab) | Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab) |
|---|---|---|
| Cycle 1 Day 1; Pre-dose | NA ± NA | — |
| Cycle 1 Day 1; 4 Hours Post-dose | 328 ± 254 | — |
| Cycle 2; Pre-dose | 669 ± 503 | — |
| Cycle 2; 4 Hours Post-dose | 967 ± 540 | — |
| Cycle 4; Pre-dose | 486 ± 243 | — |
| Cycle 4; 4 Hours Post-dose | 795 ± 228 | — |
| Cycle 9; Pre-dose | 456 ± 134 | — |
| Cycle 9; 4 Hours Post-dose | 766 ± 231 | — |
Overall survival was defined as the time from date of first dose to the date of death due to any cause.
No measurements were reported for this outcome.
Overall survival was defined as the time from date of first dose to the date of death due to any cause.
No measurements were reported for this outcome.
Overall survival was defined as the time from date of first dose to the date of death due to any cause.
No measurements were reported for this outcome.
Overall survival was defined as the time from date of first dose to the date of death due to any cause.
No measurements were reported for this outcome.
Collected over All-cause mortality serious adverse events (SAE) and non-SAE were collected up to a maximum of 45 months in Cohort 1-Stage 1,up to a maximum of 17 months in Cohort 2-Stage 1,up to a maximum of 6 months in Cohort 3-Stage 1 and up to a maximum of 29 months in Cohort 1A-Stage 2.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Stage 1 (Cohort 1): Niraparib + Pembrolizumab | 11/17 (64.7%) | 11/17 (64.7%) | 17/17 (100%) |
| Stage 1 (Cohort 2): Niraparib + Pembrolizumab | 16/21 (76.2%) | 14/21 (66.7%) | 20/21 (95.2%) |
| Stage 1 (Cohort 3): Niraparib | 1/3 (33.3%) | 1/3 (33.3%) | 3/3 (100%) |
| Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab) | 6/12 (50%) | 7/12 (58.3%) | 12/12 (100%) |
| Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab) | — | — | — |
| Event | Stage 1 (Cohort 1): Niraparib + Pembrolizumab | Stage 1 (Cohort 2): Niraparib + Pembrolizumab | Stage 1 (Cohort 3): Niraparib | Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab) | Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab) |
|---|---|---|---|---|---|
| Respiratory failureRespiratory, thoracic and mediastinal disorders | 0/17 | 1/21 | 1/3 | 2/12 | — |
| Small intestinal obstructionGastrointestinal disorders | 0/17 | 0/21 | 1/3 | 0/12 | — |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 1/17 | 4/21 | 0/3 | 0/12 | — |
| PneumoniaInfections and infestations | 3/17 | 3/21 | 0/3 | 2/12 | — |
| AnaemiaBlood and lymphatic system disorders | 2/17 | 1/21 | 0/3 | 0/12 | — |
| Mental status changesPsychiatric disorders | 2/17 | 0/21 | 0/3 | 0/12 | — |
| Pleural effusionRespiratory, thoracic and mediastinal disorders | 0/17 | 2/21 | 0/3 | 0/12 | — |
| Atrial fibrillationCardiac disorders | 0/17 | 2/21 | 0/3 | 0/12 | — |
| Pulmonary embolismRespiratory, thoracic and mediastinal disorders | 1/17 | 1/21 | 0/3 | 1/12 | — |
| Acute respiratory failureRespiratory, thoracic and mediastinal disorders | 0/17 | 0/21 | 0/3 | 1/12 | — |
| Event | Stage 1 (Cohort 1): Niraparib + Pembrolizumab | Stage 1 (Cohort 2): Niraparib + Pembrolizumab | Stage 1 (Cohort 3): Niraparib | Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab) | Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab) |
|---|---|---|---|---|---|
| NauseaGastrointestinal disorders | 7/17 | 12/21 | 2/3 | 7/12 | — |
| Nasal congestionRespiratory, thoracic and mediastinal disorders | 2/17 | 1/21 | 2/3 | 1/12 | — |
| Decreased appetiteMetabolism and nutrition disorders | 7/17 | 11/21 | 1/3 | 4/12 | — |
| DiarrhoeaGastrointestinal disorders | 4/17 | 3/21 | 0/3 | 6/12 | — |
| ConstipationGastrointestinal disorders | 7/17 | 10/21 | 1/3 | 4/12 | — |
| AnaemiaBlood and lymphatic system disorders | 4/17 | 10/21 | 0/3 | 2/12 | — |
| FatigueGeneral disorders | 8/17 | 9/21 | 1/3 | 5/12 | — |
| Oedema peripheralGeneral disorders | 2/17 | 5/21 | 0/3 | 5/12 | — |
| CoughRespiratory, thoracic and mediastinal disorders | 7/17 | 3/21 | 1/3 | 2/12 | — |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 4/17 | 8/21 | 0/3 | 1/12 | — |
Data was not collected for Cohort 2A of Stage 2 as no participant was enrolled into this Cohort of the study. Safety Population comprised of participants who received at least one dose of either study medications.
| Age, Continuous(Years) | Stage 1 (Cohort 1): Niraparib + Pembrolizumab | Stage 1 (Cohort 2): Niraparib + Pembrolizumab | Stage 1 (Cohort 3): Niraparib | Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab) | Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab) | Total |
|---|---|---|---|---|---|---|
| Mean | 70.1 ± 7.55 | 70.9 ± 9.78 | 72.3 ± 10.69 | 68.3 ± 6.74 | — | 70.1 ± 8.35 |
| Sex: Female, Male(Participants) | Stage 1 (Cohort 1): Niraparib + Pembrolizumab | Stage 1 (Cohort 2): Niraparib + Pembrolizumab | Stage 1 (Cohort 3): Niraparib | Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab) | Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab) | Total |
|---|---|---|---|---|---|---|
| Female | 6 | 12 | 0 | 6 | — | 24 |
| Male | 11 | 9 | 3 | 6 | — | 29 |
| Race/Ethnicity, Customized(Participants) | Stage 1 (Cohort 1): Niraparib + Pembrolizumab | Stage 1 (Cohort 2): Niraparib + Pembrolizumab | Stage 1 (Cohort 3): Niraparib | Stage 2 (Cohort 1A): Niraparib + TSR-042 (Dostarlimab) | Stage 2 (Cohort 2A): Niraparib + TSR-042 (Dostarlimab) | Total |
|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 1 | — | 1 |
| Asian | 0 | 1 | 0 | 1 | — | 2 |
| Black or African American | 1 | 0 | 0 | 2 | — | 3 |
| White | 14 | 19 | 3 | 8 | — | 44 |
| Unknown | 2 | 1 | 0 | 0 | — | 3 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
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.com
Ran from Sep 2017 to primary completion in May 2020, 31 months.
Results were first posted in Jul 2021, 1 year 2 months after primary completion.
Of 179 industry-sponsored phase 2 interventional studies under Neoplasms, half reached primary completion within 42 months of starting (the median), counting those still running; a quarter within 26 and three quarters within 68. This study's 31 months is below that.
Counting every sponsor, half of 514 studies reached it within 52 months; a quarter within 33 and three quarters within 92.
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 Oct 2023. You cannot join it, but the record below documents what was studied.
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Studies of the drugs tested here: Niraparib · Dostarlimab