A Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab in Participants 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.

Time frame: Up to approximately 31 months

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

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.

Time frame: At 16 weeks

Population: The ITT population included all participants enrolled in the study.

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.

Time frame: Up to approximately 22 months

Population: 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.

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

Time frame: Day 15 of Cycle 3 (cycle is 28 days): 2-4 hours after cobimetinib dose

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

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

Time frame: 30 minutes following end of atezolizumab infusion on Day 15 of Cycle 3 (each cycle is 28 days)

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

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

Time frame: Day 15 of Cycle 3 (cycle is 28 days): prior to cobimetinib dose

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

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

Time frame: Prior to atezolizumab infusion on Day 1 of Cycles (each cycle is 28 days) 2, 4, 8, 12, and 16, Day 15 of Cycle 3

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

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.

Time frame: Up to approximately 31 months

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

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).

Time frame: Day 1 of Cycles (each cycle is 28 days) 1, 2, 4, 8, 12, and 16; Day 15 of Cycle 3; at atezolizumab treatment discontinuation visit, and <90 days after last atezolizumab infusion (up to approximately 31 months)

Population: 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.

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.

Time frame: Up to approximately 31 months

Population: The ITT population included all participants enrolled in the study.

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.

Time frame: Up to approximately 31 months

Population: The ITT population included all participants enrolled in the study.