Antineoplastic Agents

All Drugs and Chemicals

Atezolizumab

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Immunologic Factors

In participants with recurrent or advanced / metastatic SSCHN who are anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

In participants with advanced / metastatic UC who are anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

In participants with metastatic RCC who are anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib will be administered at the approved dose and schedule of 60 milligrams (mg) once daily (QD) for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

In participants with SCCHN whose disease has progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

In participants with UC whose disease has progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

In participants with RCC whose disease has progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

In participants with solid non-melanoma, non- hematologic tumors who previously developed primary or secondary resistance to an anti-PD-1 or anti-PD-L1 agent, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle. The first dose of atezolizumab of 840 mg by IV infusions on Day 15 of Cycle 1. Thereafter, they will receive atezolizumab 840 mg IV infusion Q2W on Days 1 and 15 of Cycle 2 and all subsequent cycles.

Participants will receive cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1-21 of each 28-day cycle.

Cobimetinib

Atezolizumab will be given at a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

Only for participants in cohort 7, the first dose of atezolizumab of 840 mg will be given by IV infusion on Day 15 of Cycle 1; thereafter, they will receive atezolizumab 840 mg IV infusion Q2W on Days 1 and 15 of Cycle 2 and all subsequent cycles.

Atezolizumab Cohort 7

Clinical Trials

This is a study to evaluate the efficacy, safety, and pharmacokinetics of cobimetinib plus atezolizumab in participants with advanced solid tumors including the following cohorts: squamous cell carcinoma of the head and neck (SCCHN), urothelial carcinoma (UC), and renal cell carcinoma (RCC).

A Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab in Participants With Solid Tumors

A Phase II, Open-Label, Multicenter, Multicohort Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab in Patients With Solid Tumors

Objective response rate was defined as the percentage of participants with a complete response (CR) or a partial response (PR) on two consecutive tumor assessments ≥4 weeks apart, as determined by the investigators using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). CR was defined as disappearance of all lesions. PR was defined as ≥30% decrease in the sum of diameters of target lesions, in the absence of CR, new lesions, and unequivocal progression in non-target lesions.

Overall survival was defined as the time from enrollment to death from any cause. The median for OS is Kaplan-Meier estimate. 95% CI for median was computed using the method of Brookmeyer and Crowley.

PFS was defined as the time from enrollment to the first occurrence of disease progression as determined by the investigator(s), using RECIST v1.1, or to death from any cause, whichever occurs first. Disease progression was defined as ≥20% increase in in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions.

DOR was defined as the time from the first occurrence of a documented, confirmed objective response to disease progression as determined by the investigator, using RECIST v1.1, or to death from any cause, whichever occurs first. Objective response was defined as a complete response (CR) or a partial response (PR) on two consecutive tumor assessments ≥4 weeks apart. CR was defined as disappearance of all lesions. PR was defined as ≥30% decrease in the sum of diameters of target lesions, in the absence of CR, new lesions, and unequivocal progression in non-target lesions. Disease progression was defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions. Presented here is median DOR at the time of primary analysis. The median for the duration of response is Kaplan-Meier estimate. 95% CI for median was computed using the method of Brookmeyer and Crowley.

DCR was defined as the percentage of participants with a complete response (CR), a partial response (PR), or stable disease at 16 weeks as determined by the investigator using RECIST v1.1. CR was defined as disappearance of all lesions. PR was defined as ≥30% decrease in the sum of diameters of target lesions, in the absence of CR, new lesions, and unequivocal progression in non-target lesions. Stable disease was defined as neither sufficient shrinkage to qualify for CR or PR nor sufficient increase to qualify for disease progression. Disease progression was defined as ≥20% increase in the sum of diameters of target lesions, unequivocal progression in non-target lesions, and/or appearance of new lesions.

An adverse event is any untoward medical occurrence in a subject 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.

Cmax is the maximum (or peak) concentration that a study drug achieves in the body.

Cmin is the minimum (or trough) concentration that a study drug achieves in the body.

Participants were considered to be ADA positive if they were missing data at baseline but developed an ADA response following study drug administration (treatment-induced ADA response), or if they were ADA positive at baseline and the titer of one or more post-baseline samples was at least 4-fold greater (i.e., ≥0.60-titer units) than the titer of the baseline sample (treatment-enhanced ADA response). Participants were considered to be ADA negative if they were missing data at baseline, had a post-baseline ADA result, and all post-baseline samples were negative, or if they were ADA positive at baseline but did not have any post-baseline samples with a titer that was at least 4-fold greater than the titer of the baseline sample (treatment unaffected).

Hoffmann-La Roche

The safety population included all enrolled participants who received at least one dose of study drug.

In participants with recurrent or advanced / metastatic squamous cell carcinoma of the head and neck (SSCHN) who were anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib was administered at the approved dose and schedule of 60 mg once daily (QD) for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

Cohort 1 - SCCHN - Treatment Naive

In participants with advanced / metastatic urothelial carcinoma (UC) who were anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

Cohort 2 - UC - Treatment Naive

In participants with metastatic renal cell carcinoma (RCC) who were anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

Cohort 3 - RCC - Treatment Naive

In participants with SCCHN whose disease had progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

Cohort 4 - SCCHN - Previous Treatment Exposure

In participants with UC whose disease had progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

Cohort 5 - UC - Previous Treatment Exposure

In participants with RCC whose disease had progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

Cohort 6 - RCC - Previous Treatment Exposure

Total

Age, Customized

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

The intent-to-treat (ITT) population included all participants enrolled in the study.

Medical Communications

Objective Response Rate (ORR)

The ITT population included all participants enrolled in the study.

Overall Survival (OS)

Progression-Free Survival (PFS)

ITT population: all participants enrolled in the study. Median DOR is presented at the time of primary analysis. DOR analyses were not performed at final analysis because Kaplan-Meier was not estimable at primary analysis due to too few events in Cohorts 1 and 3. There were no subsequent events in Cohorts 1 and 3. Cohorts 4-6 had no events.

Duration of Response (DOR)

Disease Control Rate (DCR)

Number of Participants With Adverse Events

In all participants cobimetinib was administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by IV infusion on Days 1 and 15 of each 28-day cycle.

Cohorts 1-6

Pharmacokinetic (PK) analysis population consisted of participants with sufficient data to enable estimation of key parameters, with participants grouped according to treatment received.

Maximum Plasma Concentration (Cmax) of Cobimetinib

PK analysis population consisted of participants with sufficient data to enable estimation of key parameters, with participants grouped according to treatment received.

Minimum Plasma Concentration (Cmin) of Cobimetinib

Maximum Serum Concentration (Cmax) of Atezolizumab

Minimum Serum Concentration (Cmin) of Atezolizumab

The safety population included all enrolled participants who received at least one dose of study drug. Number analyzed is the number of participants with data available for analysis.

Spots Global Cancer Trial Database for A Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab in Participants With Solid Tumors

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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