A Study of Cobimetinib Plus Atezolizumab Versus Pembrolizumab in Participants With Previously Untreated Advanced BRAFv600 Wild-Type Melanoma

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

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.

Population: The analysis population for this endpoint was the patient reported outcome (PRO) population evaluable participants for EORTC QLQ-C30.

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

Population: The analysis for this outcome measure was limited to participants meeting the criteria provided in the description.

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

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

Vital signs will include temperature, pulse rate, respiratory rate, and systolic and diastolic blood pressure.

Time frame: From baseline up to approximately 3 years

Population: N for each assessment = participants without abnormalities at baseline or with missing baseline values

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

Participants with laboratory abnormalities (values outside of a defined range) will be reported.

Time frame: Up to approximately 16 months

Population: Participants with at least one post-baseline assessment for a given laboratory value were included in this assessment.

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

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

OS is defined as the time from randomization to death from any cause.

Time frame: From randomization up to approximately 3 years

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

Population: Only participants from the Cobimetinib and Atezolizumab arm are included in this endpoint as it is meant to evaluate the immune response to atezolizumab.

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

Time frame: Days 1 and 15 of Cycle 1

Population: PK data was not available from all participants at all time points due to study continuation or missed PK sampling.

Time frame: Day 1 of Cycles 1, 2, and 3

Population: PK data was not available from all participants at all time points due to study continuation or missed PK sampling.

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