A Phase 3 interventional study of Cobimetinib and Atezolizumab in Advanced BRAFV600 Wild-type Melanoma, sponsored by Hoffmann-La Roche. Terminated at 121 sites in 15 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-09-21.
Sponsored by Hoffmann-La Roche · Phase 3, Interventional, and Treatment
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Among 27 studies testing cobimetinib in Melanoma — 3 open to participants now, 6 under way, 1 of them phase 3. cobimetinib · Melanoma.
Among the 27 studies testing cobimetinib in Melanoma, this one is the 2nd largest by enrollment, is one of 4 that started in 2017, is one of 3 in phase 3, and was the 18th registered.
3,372 studies on the registry are indexed under Melanoma; 580 are open to participants now.
Browse Melanoma studies →3 of the 27 studies testing cobimetinib in Melanoma are open now, in 3 countries. Recruiting first, the newest first:
Hanmi Pharmaceutical Company Limited · Sites in Korea, Republic of
Ages 19+
N.N. Petrov National Medical Research Center of Oncology · Sites in Russian Federation
Ages 18–85 · Healthy volunteers
Cancer Research UK · Sites in United Kingdom
Ages 18+
By country, each count listing its studies:
cobimetinib: first FDA approval 2015 (COTELLIC), first EMA approval 2015. What it is approved for, and how studies give it, is on its page →
Of the 468 Melanoma studies recruiting now, 381 (81%) set no upper age limit and 49 (10%) stop at 75 or younger; 47 take children under 18; 29 take healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
On this site’s reading of the record, cobimetinib is the treatment under test here. Read study by study →
27 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 5 · Phase 2 19 · Phase 3 4
First in 2011; this study’s year is marked. 4 started in 2017.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 446 is above the median of 40 across 2,650 interventional studies indexed under Melanoma.
Median enrollment 45 across the 27 interventional studies. Of the 17 that completed or were terminated, 9 (53%) have results posted.
This tab as a report to print or save as PDF → With an account.
8 of 27 have an industry lead sponsor. The 10 most frequent:
Hoffmann-La Roche is the lead sponsor of 2,101 studies on the registry; 88 are open to participants now.
Of its 330 completed or terminated interventional studies of FDA-regulated products, 248 (75%) have results posted.
57 studies in Melanoma by Hoffmann-La Roche: none open now, 4 under way, none of them phase 3. Of 52 finished, 34 (65%) have results posted.
Among the 57 studies in Melanoma by Hoffmann-La Roche, this one is the 7th largest by enrollment of the 52 interventional ones that give a count, is one of 4 that started in 2017, is one of 6 in phase 3, and was the 43rd registered.
Hoffmann-La Roche’s Melanoma studies by the year they started, since 2004.
1 of the studies testing cobimetinib in Melanoma that are under way reach primary completion within a year, 0 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT04835805Genentech, Inc.A Study to Evaluate the Safety and Activity of Belvarafenib as a Single Agent and in Combination With Either Cobimetinib or Cobimetinib Plus Nivolumab in Patients With NRAS-mutant Advanced Melanoma. | 2026-12-31 |
Add it to your calendar (.ics) → With an account.
Among the 27 studies testing cobimetinib in Melanoma, from their registry updates:
Nothing recorded among them since 2026-09-25.
Among Hoffmann-La Roche’s 57 in Melanoma:
Nothing recorded among them since 2026-09-25.
This tab as a report to print or save as PDF → With an account.
This is a Phase III, multicenter, open-label, randomized study designed to evaluate the efficacy, safety, and pharmacokinetics of cobimetinib plus atezolizumab compared with pembrolizumab in treatment-naive participants with advanced BRAFV600 wild-type melanoma.
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.
Disease-Specific Inclusion Criteria
Exclusion Criteria:
General Exclusion Criteria
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.
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
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.
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 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.
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.
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.
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.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
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.
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.
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.
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.
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.
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Histologically or cytologically confirmed
The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).
Your pathology report is the document that shows this.
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.
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.
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.
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.
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.
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.
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.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
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.
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.
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.
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.
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.
TIA (transient ischaemic attack)
A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.
Stroke symptoms need emergency care at once, even if they go away.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Participants will receive 60 mg of cobimetinib orally from Days 1 to 21 along with 840 mg of atezolizumab by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurs first. There will be no cobimetinib administration for 7 days (Days 22-28) in each cycle.
Drug: Cobimetinib · Drug: Atezolizumab
Participants will receive 200 mg of pembrolizumab administered by IV infusion every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurs first.
Drug: Pembrolizumab
Cobimetinib 60 mg tablets orally once daily on a 21 days on, 7 days off schedule.
Atezolizumab 840 mg as IV infusion once in every 2 weeks.
Pembrolizumab 200 mg as IV infusion once in every 3 weeks.
Progression Free Survival (PFS) as Determined by the Independent Review Committee (IRC)
PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by an IRC according to RECIST v1.1, or death from any cause, whichever occurs first. Progressive disease (PD) for target lesion: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/=5 mm. PD for non-target lesion: Unequivocal progression of existing non-target lesions.
Time frame: Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
PFS as Determined by the Investigator
PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. Progressive disease (PD) for target lesion: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/=5 mm. PD for non-target lesion: Unequivocal progression of existing non-target lesions.
Time frame: Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
Objective Response as Determined by the Investigator
Objective response rate is defined as the percentage of participants with a complete response (CR) or a partial response (PR) on two consecutive occasions \>/=4 weeks apart, as determined by the investigator through the use of RECIST v1.1. For target lesion, CR: the disappearance of all target lesions, any pathological lymph nodes must have a reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. For non-target lesion, CR: the disappearance of all non-target lesions and (if applicable) normalization of tumor marker level, all lymph nodes must be non-pathological in size (\<10 mm short axis).
Time frame: Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
Objective Response as Determined by IRC
Objective response, defined as a complete response or partial response on two consecutive occasions ≥4 weeks apart, as determined by IRC according to RECIST v1.1
Time frame: Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
Disease Control Rate (DCR)
DCR is defined as the proportion of participants with a complete response, a partial response, or stable disease at 16 weeks. For target lesion, CR: the disappearance of all target lesions, any pathological lymph nodes must have a reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. For non-target lesion, CR: the disappearance of all non-target lesions and (if applicable) normalization of tumor marker level, all lymph nodes must be non-pathological in size (\<10 mm short axis). Stable disease (SD): neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD.
Time frame: Week 16
Overall Survival (OS)
OS is defined as the time from randomization to death from any cause.
Time frame: From randomization up to approximately 3 years
Duration of Objective Response Determined by the IRC
Duration of objective response, defined as the time from the first occurrence of a documented objective response to disease progression, as determined by an IRC according to RECIST v1.1, or death from any cause, whichever occurs first.
Time frame: Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
Duration of Objective Response Determined by the Investigator
Duration of objective response is defined as the time from the first occurrence of a documented objective response to disease progression, as determined by the investigator through use of RECIST v1.1, or death from any cause, whichever occurs first.
Time frame: Up to 3 years
Two-year Landmark Survival
Two-year landmark survival is defined as the rate of survival at 2 years. Two-year landmark survival is defined as the rate of survival at 2 years and was calculated using Kaplan-Meier analysis, which is commonly used to estimate the probability of an event at time 't.'
Time frame: At 2 years
Change From Baseline in Health-related Quality of Life (HRQoL) Scores
HRQoL scores are assessed through global health status (GHS)/ quality of life (QoL) subscale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30). These are based on questions 29 and 30 of the EORTC QLQ-C30. These questions on global health status/QoL scale are coded on 7-point scale (1=very poor to 7=excellent). Raw scores will be linearly transformed to obtain the score ranging from 0 to 100, where higher score represents a higher ("better") level of functioning.
Time frame: Up to approximately 16 months. Follow up is reported at weeks after participant treatment discontinuation, which could occur at any time during the study. Total time frame does not exceed 16 months.
Number of Participants With Adverse Events (AEs)
An adverse event is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
Time frame: Up to approximately 16 months
Number of Participants With Abnormal Vital Signs
Vital signs will include temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure.
Time frame: From baseline up to approximately 3 years
Number of Participants With Laboratory Abnormalities
Participants with laboratory abnormalities (values outside of a defined range) will be reported.
Time frame: Up to approximately 16 months
Plasma Concentration of Cobimetinib
Time frame: Days 1 and 15 of Cycle 1
Serum Concentration of Atezolizumab
Time frame: Day 1 of Cycles 1, 2, and 3
Percentage of Participants With Anti-drug Antibodies (ADAs)
Participants with ADAs during the study relative to the prevalence of ADAs at baseline will be reported.
Time frame: Day 1 of Cycle 1, 2, 3 and 30 days after treatment discontinuation
| Milestone | Pembrolizumab | Cobimetinib and Atezolizumab |
|---|---|---|
| Started | 224 | 222 |
| Completed | 0 | 0 |
| Not completed | 224 | 222 |
| Withdrew: Adverse event | 1 | 2 |
| Withdrew: Missing | 0 | 2 |
| Withdrew: Other | 3 | 2 |
| Withdrew: Symptomatic deterioration | 0 | 1 |
| Withdrew: Progressive disease | 6 | 5 |
| Withdrew: Physician decision | 1 | 3 |
| Withdrew: Study terminated by sponsor | 112 | 102 |
| Withdrew: Withdrawal by subject | 26 | 25 |
| Withdrew: Protocol deviation | 3 | 0 |
| Withdrew: Lost to follow-up | 6 | 11 |
| Withdrew: Death | 66 | 69 |
PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by an IRC according to RECIST v1.1, or death from any cause, whichever occurs first. Progressive disease (PD) for target lesion: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/=5 mm. PD for non-target lesion: Unequivocal progression of existing non-target lesions.
| Months | Pembrolizumab | Cobimetinib and Atezolizumab |
|---|---|---|
| Progression Free Survival (PFS) as Determined by the Independent Review Committee (IRC) | 5.7 (3.7 to 9.6) | 5.5 (3.8 to 7.2) |
PFS is defined as the time from randomization to the first occurrence of disease progression, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. Progressive disease (PD) for target lesion: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters on study (including baseline). In addition to the relative increase of 20%, the sum of diameters must also demonstrate an absolute increase of \>/=5 mm. PD for non-target lesion: Unequivocal progression of existing non-target lesions.
| Months | Pembrolizumab | Cobimetinib and Atezolizumab |
|---|---|---|
| PFS as Determined by the Investigator | 7.2 (3.8 to 10.1) | 5.6 (3.9 to 6.6) |
Objective response rate is defined as the percentage of participants with a complete response (CR) or a partial response (PR) on two consecutive occasions \>/=4 weeks apart, as determined by the investigator through the use of RECIST v1.1. For target lesion, CR: the disappearance of all target lesions, any pathological lymph nodes must have a reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. For non-target lesion, CR: the disappearance of all non-target lesions and (if applicable) normalization of tumor marker level, all lymph nodes must be non-pathological in size (\<10 mm short axis).
| Percentage of Participants | Pembrolizumab | Cobimetinib and Atezolizumab |
|---|---|---|
| Objective Response as Determined by the Investigator | 36.7 (30.29 to 43.38) | 27.9 (22.13 to 34.32) |
Objective response, defined as a complete response or partial response on two consecutive occasions ≥4 weeks apart, as determined by IRC according to RECIST v1.1
| Percentage of Participants | Pembrolizumab | Cobimetinib and Atezolizumab |
|---|---|---|
| Objective Response as Determined by IRC | 31.6 (25.27 to 38.38) | 26.0 (20.11 to 32.57) |
DCR is defined as the proportion of participants with a complete response, a partial response, or stable disease at 16 weeks. For target lesion, CR: the disappearance of all target lesions, any pathological lymph nodes must have a reduction in short axis to \<10 mm. PR: at least a 30% decrease in the sum of diameters of all target lesions, taking as reference the baseline sum of diameters, in the absence of CR. For non-target lesion, CR: the disappearance of all non-target lesions and (if applicable) normalization of tumor marker level, all lymph nodes must be non-pathological in size (\<10 mm short axis). Stable disease (SD): neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for PD.
| Percentage of Participants | Pembrolizumab | Cobimetinib and Atezolizumab |
|---|---|---|
| Investigator-assessed | 49.8 (43.00 to 56.56) | 46.8 (40.14 to 53.64) |
| IRC-assessed | 44.2 (37.28 to 51.24) | 45.6 (38.62 to 52.69) |
OS is defined as the time from randomization to death from any cause.
| Months | Pembrolizumab | Cobimetinib and Atezolizumab |
|---|---|---|
| Overall Survival (OS) | 29.3 (21.5 to NA) | NA (24.1 to NA) |
Duration of objective response, defined as the time from the first occurrence of a documented objective response to disease progression, as determined by an IRC according to RECIST v1.1, or death from any cause, whichever occurs first.
| Months | Pembrolizumab | Cobimetinib and Atezolizumab |
|---|---|---|
| Duration of Objective Response Determined by the IRC | NA (NA to NA) | NA (9.2 to NA) |
Duration of objective response is defined as the time from the first occurrence of a documented objective response to disease progression, as determined by the investigator through use of RECIST v1.1, or death from any cause, whichever occurs first.
| Months | Pembrolizumab | Cobimetinib and Atezolizumab |
|---|---|---|
| Duration of Objective Response Determined by the Investigator | NA (NA to NA) | NA (9.2 to NA) |
Two-year landmark survival is defined as the rate of survival at 2 years. Two-year landmark survival is defined as the rate of survival at 2 years and was calculated using Kaplan-Meier analysis, which is commonly used to estimate the probability of an event at time 't.'
| Percentage | Pembrolizumab | Cobimetinib and Atezolizumab |
|---|---|---|
| Two-year Landmark Survival | 57.88 (48.25 to 67.52) | 60.19 (51.58 to 68.79) |
HRQoL scores are assessed through global health status (GHS)/ quality of life (QoL) subscale of the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C30). These are based on questions 29 and 30 of the EORTC QLQ-C30. These questions on global health status/QoL scale are coded on 7-point scale (1=very poor to 7=excellent). Raw scores will be linearly transformed to obtain the score ranging from 0 to 100, where higher score represents a higher ("better") level of functioning.
| Units on a Scale | Pembrolizumab | Cobimetinib and Atezolizumab |
|---|---|---|
| Baseline value | 73.27 ± 20.41 | 73.85 ± 19.73 |
| Week 4 | -2.99 ± 17.05 | -9.14 ± 20.83 |
| Week 8 | -3.15 ± 18.67 | -5.21 ± 18.18 |
| Week 12 | -1.77 ± 19.93 | -7.65 ± 21.20 |
| Week 16 | 1.16 ± 15.02 | -6.44 ± 20.58 |
| Week 20 | 1.69 ± 17.50 | -6.31 ± 19.17 |
| Week 24 | -1.84 ± 19.82 | -2.49 ± 15.98 |
| Week 28 | 2.46 ± 19.07 | -3.86 ± 19.10 |
| Week 32 | -0.88 ± 22.41 | -4.66 ± 20.94 |
| Week 36 | 4.17 ± 20.56 | -6.00 ± 18.24 |
| Week 40 | 7.22 ± 19.38 | -4.63 ± 21.62 |
| Week 44 | 0.46 ± 19.27 | 1.67 ± 12.91 |
| Week 48 | 7.64 ± 13.04 | 0.00 ± 15.96 |
| Week 52 | 1.67 ± 12.36 | 8.33 ± 15.21 |
| Week 56 | -11.11 ± 17.21 | -2.08 ± 4.17 |
| Week 60 | -8.33 ± 11.79 | -4.17 ± 5.89 |
| Week 64 | 33.33 ± NA | — |
| Treatment Discontinuation | -6.05 ± 22.53 | -14.42 ± 25.68 |
| Follow-up 4 | -7.64 ± 14.85 | -2.27 ± 18.67 |
| Follow-up 8 | -14.25 ± 21.96 | -14.10 ± 24.15 |
| Follow-up 12 | -21.38 ± 24.34 | -24.31 ± 28.08 |
| Follow-up 16 | -13.73 ± 19.53 | -23.61 ± 23.26 |
| Follow-up 20 | -20.83 ± 26.53 | -8.33 ± 12.91 |
| Follow-up 24 | -17.71 ± 29.36 | -10.00 ± 14.91 |
| Follow-up 28 | -27.78 ± 22.15 | -16.67 ± 23.57 |
An adverse event is any untoward medical occurrence in a patient administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
| Number of Participants | Pembrolizumab | Cobimetinib and Atezolizumab |
|---|---|---|
| Number of Participants With Adverse Events (AEs) | 195 | 218 |
Vital signs will include temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure.
| Participants | Pembrolizumab | Cobimetinib and Atezolizumab |
|---|---|---|
| Sitting diastolic blood pressure - low | 41 | 42 |
| Sitting diastolic blood pressure - high | 77 | 85 |
| Sitting systolic blood pressure - low | 4 | 7 |
| Sitting systolic blood pressure - high | 53 | 47 |
| Pulse rate - low | 58 | 67 |
| Pulse rate - high | 13 | 27 |
| Respiratory rate - low | 8 | 11 |
| Respiratory rate - high | 55 | 52 |
| Temperature - low | 91 | 93 |
| Temperature - high | 20 | 47 |
Participants with laboratory abnormalities (values outside of a defined range) will be reported.
| Number of Participants | Pembrolizumab | Cobimetinib and Atezolizumab |
|---|---|---|
| SGPT/ALT | 1 | 1 |
| Amylase | 4 | 5 |
| SGOT/AST | 0 | 2 |
| Calcium | 0 | 1 |
| Creatine Kinase | 1 | 17 |
| Creatinine | 1 | 4 |
| Glucose | 8 | 13 |
| Triacylglycerol Lipase | 8 | 10 |
| Magnesium | 3 | 2 |
| Phosphorus | 6 | 10 |
| Potassium | 1 | 6 |
| Sodium | 2 | 4 |
| Uric Acid | 36 | 30 |
| Hemoglobin | 2 | 2 |
| Lymphocytes Abs | 6 | 15 |
| Neutrophils, Total, Abs | 0 | 1 |
| Total Leukocyte Count | 3 | 0 |
| nanograms/mL | Cobimetinib and Atezolizumab |
|---|---|
| Cycle 1 Day 1 | 49.2 ± 614.7 |
| Cycle 1 Day 15 pre-dose | 126 ± 284.1 |
| Cycle 1 Day 15 post-dose | 231 ± 213.3 |
| micrograms/mL | Cobimetinib and Atezolizumab |
|---|---|
| Cycle 1 Day 1 | 256 ± 35.3 |
| Cycle 2 Day 1 | 72.2 ± 177.1 |
| Cycle 3 Day 1 | 126 ± 104.3 |
Participants with ADAs during the study relative to the prevalence of ADAs at baseline will be reported.
| Percentage of participants | Cobimetinib and Atezolizumab |
|---|---|
| Percentage of Participants With Anti-drug Antibodies (ADAs) | 23.2 |
Collected over For up to 135 days after the last dose of study drug, or until a new systemic anti-cancer therapy was initiated, whichever occurred first (a maximum of approximately 3 years).. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Pembrolizumab | 68/224 (30.4%) | 56/216 (25.9%) | 173/216 (80.1%) |
| Cobimetinib and Atezolizumab | 70/222 (31.5%) | 105/220 (47.7%) | 209/220 (95%) |
| Event | Pembrolizumab | Cobimetinib and Atezolizumab |
|---|---|---|
| PyrexiaGeneral disorders | 2/216 | 12/220 |
| DiarrhoeaGastrointestinal disorders | 2/216 | 9/220 |
| SepsisInfections and infestations | 0/216 | 6/220 |
| Pulmonary embolismRespiratory, thoracic and mediastinal disorders | 5/216 | 3/220 |
| VomitingGastrointestinal disorders | 0/216 | 5/220 |
| AstheniaGeneral disorders | 3/216 | 4/220 |
| RashSkin and subcutaneous tissue disorders | 1/216 | 4/220 |
| RhabdomyolysisMusculoskeletal and connective tissue disorders | 0/216 | 4/220 |
| Abdominal pain upperGastrointestinal disorders | 3/216 | 1/220 |
| PancreatitisGastrointestinal disorders | 3/216 | 1/220 |
| Event | Pembrolizumab | Cobimetinib and Atezolizumab |
|---|---|---|
| DiarrhoeaGastrointestinal disorders | 42/216 | 120/220 |
| RashSkin and subcutaneous tissue disorders | 27/216 | 90/220 |
| Blood creatine phosphokinase increasedInvestigations | 13/216 | 81/220 |
| PyrexiaGeneral disorders | 17/216 | 65/220 |
| AstheniaGeneral disorders | 42/216 | 59/220 |
| NauseaGastrointestinal disorders | 28/216 | 54/220 |
| Oedema peripheralGeneral disorders | 17/216 | 50/220 |
| Dermatitis acneiformSkin and subcutaneous tissue disorders | 3/216 | 50/220 |
| PruritisSkin and subcutaneous tissue disorders | 35/216 | 44/220 |
| FatigueGeneral disorders | 42/216 | 43/220 |
| Age, Continuous(Years) | Pembrolizumab | Cobimetinib and Atezolizumab | Total |
|---|---|---|---|
| Mean | 63.5 ± 12.9 | 63.6 ± 13.1 | 63.6 ± 13.0 |
| Sex: Female, Male(Participants) | Pembrolizumab | Cobimetinib and Atezolizumab | Total |
|---|---|---|---|
| Female | 83 | 93 | 176 |
| Male | 141 | 129 | 270 |
| Ethnicity (NIH/OMB)(Participants) | Pembrolizumab | Cobimetinib and Atezolizumab | Total |
|---|---|---|---|
| Hispanic or Latino | 7 | 15 | 22 |
| Not Hispanic or Latino | 190 | 180 | 370 |
| Unknown or Not Reported | 27 | 27 | 54 |
| Race (NIH/OMB)(Participants) | Pembrolizumab | Cobimetinib and Atezolizumab | Total |
|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 |
| Asian | 6 | 6 | 12 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 |
| Black or African American | 1 | 6 | 7 |
| White | 198 | 188 | 386 |
| More than one race | 0 | 0 | 0 |
| Unknown or Not Reported | 19 | 22 | 41 |
Showing the first 100 of 121 sites across 15 countries. Choose a country and city above to see the rest.
PDFs hosted by the registry, ClinicalTrials.gov.
Ran from Dec 2017 to primary completion in Apr 2019, 16 months.
Results were first posted in Jun 2020, 1 year 1 month after primary completion.
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Studies of the drugs tested here: Cobimetinib · Atezolizumab