A Study of Cobimetinib Plus Atezolizumab Versus Pembroliz... | NCT03273153

ID	Type	Description	Link
2016-004387-18	EudraCT Number

Status Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Cobimetinib and Atezolizumab	Experimental	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
Pembrolizumab	Active Comparator	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

Name	Type	Description	Arm Group Labels	Other Names
Cobimetinib	Drug	Cobimetinib 60 mg tablets orally once daily on a 21 days on, 7 days off schedule.	Cobimetinib and Atezolizumab

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months

Secondary Outcomes

Measure	Description	Time Frame
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.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Disease-Specific Inclusion Criteria

Histologically confirmed locally advanced and unresectable or metastatic melanoma
Naive to prior systemic anti-cancer therapy for melanoma
Documentation of BRAFV600 wild-type status in melanoma tumor tissue through use of a clinical mutation test approved by the local health authority
A representative, formalin-fixed, paraffin-embedded (FFPE) tumor specimen in a paraffin block (preferred) or 20 slides containing unstained, freshly cut, serial sections must be submitted along with an associated pathology report prior to study entry. If 20 slides are not available or the tissue block is not of sufficient size, the patient may still be eligible for the study, after discussion with and approval by the Medical Monitor
Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Age >=18 years at time of signing Informed Consent Form
Ability to comply with the study protocol, in the investigator's judgment
Histologically or cytologically confirmed BRAFV600 wild-type melanoma
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Life expectancy >=3 months
Adequate hematologic and end-organ function
For women of childbearing potential: agreement to remain abstinent or use at least two forms of effective contraceptive with a failure rate of < 1% per year during the treatment period and for at least 3 months after the last dose of cobimetinib and at least 5 months after the last dose of atezolizumab or pembrolizumab
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures (e.g. condom), and agreement to refrain from donating sperm, for at least 3 months after the last dose of cobimetinib
Willingness and ability of patients to report selected study outcomes (e.g., GHS and HRQoL) using an electronic device or paper backup questionnaires.

Exclusion Criteria:

General Exclusion Criteria

Inability to swallow medications
Malabsorption condition that would alter the absorption of orally administered medications
Pregnancy, breastfeeding, or intention of becoming pregnant during the study
History of severe hypersensitivity reactions to components of the cobimetinib, atezolizumab, or pembrolizumab formulations
Current or recent treatment with therapeutic antibiotics, live attenuated vaccines or systemic immunostimulatory/immunosuppresive medication
Any serious medical condition or abnormality in clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study Cancer-Related Exclusion Criteria
Ocular melanoma
Major surgery or radiotherapy within 21 days prior to Day 1 of Cycle 1 or anticipation of needing such procedure while receiving study treatment
Uncontrolled tumor-related pain
Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days
Active or untreated central nervous system (CNS) metastases Exclusions Related to Cardiovascular Disease
Unstable angina, new-onset angina within last 3 months, myocardial infarction within the last 6 months prior to Day 1 of Cycle 1, or current congestive heart failure classified as New York Heart Association Class II or higher
Left ventricular ejection fraction (LVEF) below institutional lower limit of normal or <50%, whichever is lower
Poorly controlled hypertension, defined as sustained, uncontrolled, non-episodic baseline hypertension consistently above 159/99 mmHg despite optimal medical management
History or presence of an abnormal electrocardiogram (ECG) that is clinically significant in the investigator's opinion, including complete left bundle branch block, second- or third degree heart block, or evidence of prior myocardial infarction Exclusions Related to Infections
HIV infection
Active tuberculosis infection
Severe infections within 4 weeks prior to Day 1 of Cycle 1, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
Signs or symptoms of clinically relevant infection within 2 weeks prior to Day 1 of Cycle 1
Treatment with oral or IV antibiotics within 2 weeks prior to Day 1 of Cycle 1
Active or chronic viral hepatitis B or C infection Exclusions Related to Ocular Disease
Known risk factors for ocular toxicity Exclusions Related to Autoimmune Conditions and Immunomodulatory Drugs
Active or history of autoimmune disease or immune deficiency
Prior allogeneic stem cell or solid organ transplantation
History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
Treatment with systemic immunosuppressive medications within 2 weeks prior to Day 1, Cycle 1 Exclusions Related to Other Medical Conditions or Medications
Active malignancy (other than melanoma) or a prior malignancy within the past 3 years
Any Grade >=3 hemorrhage or bleeding event within 28 days of Day 1 of Cycle 1
History of stroke, reversible ischemic neurological defect, or transient ischemic attack within 6 months prior to Day 1
Proteinuria >3.5 gm/24 hr
Consumption of foods, supplements, or drugs that are strong or moderate CYP3A4 enzyme inducers or inhibitors at least 7 days prior to Day 1 of Cycle 1 and during study treatment

Name	Affiliation	Role
Clinical Trials	Hoffmann-La Roche	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
University of Arizona Cancer Center		Tucson	Arizona	85719	United States
City of Hope Comprehensive Cancer Center

PubMed Identifier	Type	Citation	Retractions
33476492	Derived	de Azevedo SJ, de Melo AC, Roberts L, Caro I, Xue C, Wainstein A. First-line atezolizumab monotherapy in patients with advanced BRAFV600 wild-type melanoma. Pigment Cell Melanoma Res. 2021 Sep;34(5):973-977. doi: 10.1111/pcmr.12960. Epub 2021 Feb 15.

ID	Title	Description
FG000	Pembrolizumab	Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.
FG001	Cobimetinib and Atezolizumab

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot	Yes	No	No	Study Protocol	Feb 5, 2021	Feb 18, 2022

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Posted

Median

95% Confidence Interval

Months

Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months

ID	Title	Description
OG000	Pembrolizumab	Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.
OG001	Cobimetinib and Atezolizumab	Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.

Units	Counts
Participants	OG000224 OG001222

Title

Denominators

Categories

Title	Measurements
	OG0005.7(3.7 to 9.6) OG0015.5(3.8 to 7.2)

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001		Regression, Cox		0.2954		Hazard Ratio (HR)	1.15			2-Sided	95	0.88	1.50					Superiority

Secondary

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.

Posted

Median

95% Confidence Interval

Months

Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months

ID	Title	Description
OG000	Pembrolizumab	Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.
OG001	Cobimetinib and Atezolizumab	Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.

Secondary

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).

Posted

Number

95% Confidence Interval

Percentage of Participants

Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months

ID	Title	Description
OG000	Pembrolizumab	Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.
OG001	Cobimetinib and Atezolizumab	Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.

Secondary

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

Posted

Number

95% Confidence Interval

Percentage of Participants

Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months

ID	Title	Description
OG000	Pembrolizumab	Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.
OG001	Cobimetinib and Atezolizumab	Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.

Units	Counts
Participants	OG000

Secondary

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.

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

Posted

Number

95% Confidence Interval

Percentage of Participants

Week 16

ID	Title	Description
OG000	Pembrolizumab	Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.
OG001	Cobimetinib and Atezolizumab	Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.

Secondary

Overall Survival (OS)

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

Posted

Median

95% Confidence Interval

Months

From randomization up to approximately 3 years

ID	Title	Description
OG000	Pembrolizumab	Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.
OG001	Cobimetinib and Atezolizumab	Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.

Units	Counts
Participants	OG000

Secondary

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.

Posted

Median

95% Confidence Interval

Months

Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months

ID	Title	Description
OG000	Pembrolizumab	Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.
OG001	Cobimetinib and Atezolizumab	Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.

Units	Counts
Participants

Secondary

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.

Posted

Median

95% Confidence Interval

Months

Up to 3 years

ID	Title	Description
OG000	Pembrolizumab	Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.
OG001	Cobimetinib and Atezolizumab	Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.

Units	Counts
Participants	OG000

Secondary

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.'

Posted

Number

95% Confidence Interval

Percentage

At 2 years

ID	Title	Description
OG000	Pembrolizumab	Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.
OG001	Cobimetinib and Atezolizumab	Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.

Units	Counts
Participants	OG000

Secondary

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.

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

Posted

Mean

Standard Deviation

Units on a Scale

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.

ID	Title	Description
OG000	Pembrolizumab	Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.
OG001	Cobimetinib and Atezolizumab	Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.

Secondary

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.

Posted

Number

Number of Participants

Up to approximately 16 months

ID	Title	Description
OG000	Pembrolizumab	Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.
OG001	Cobimetinib and Atezolizumab	Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.

Units	Counts

Secondary

Number of Participants With Abnormal Vital Signs

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

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

Posted

Number

Participants

From baseline up to approximately 3 years

ID	Title	Description
OG000	Pembrolizumab	Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.
OG001	Cobimetinib and Atezolizumab	Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.

Units	Counts
Participants

Secondary

Number of Participants With Laboratory Abnormalities

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

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

Posted

Number

Number of Participants

Up to approximately 16 months

ID	Title	Description
OG000	Pembrolizumab	Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.
OG001	Cobimetinib and Atezolizumab	Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.

Units	Counts
Participants

Secondary

Plasma Concentration of Cobimetinib

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

Posted

Geometric Mean

Geometric Coefficient of Variation

nanograms/mL

Days 1 and 15 of Cycle 1

ID	Title	Description
OG000	Cobimetinib and Atezolizumab	Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.

Units	Counts
Participants	OG000202

Secondary

Serum Concentration of Atezolizumab

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

Posted

Geometric Mean

Geometric Coefficient of Variation

micrograms/mL

Day 1 of Cycles 1, 2, and 3

ID	Title	Description
OG000	Cobimetinib and Atezolizumab	Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.

Units	Counts
Participants	OG000196

Secondary

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.

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

Posted

Number

Percentage of participants

Day 1 of Cycle 1, 2, 3 and 30 days after treatment discontinuation

ID	Title	Description
OG000	Cobimetinib and Atezolizumab	Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.

Units	Counts
Participants	OG000

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Diarrhoea	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0002 affected216 at risk EG0019 affected220 at risk
Vomiting	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0015 affected220 at risk
Abdominal pain upper	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0003 affected216 at risk EG0011 affected220 at risk
Colitis	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0012 affected220 at risk
Nausea	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0012 affected220 at risk
Autoimmune colitis	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Haematochezia	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Haemorrhoids	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Pancreatitis	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0003 affected216 at risk EG0011 affected220 at risk
Stomatitis	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Pyrexia	General disorders	MedDRA v23.1	Non-systematic Assessment	EG0002 affected216 at risk EG00112 affected220 at risk
Asthenia	General disorders	MedDRA v23.1	Non-systematic Assessment	EG0003 affected216 at risk EG0014 affected220 at risk
Fatigue	General disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0013 affected220 at risk
General physical health deterioration	General disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0011 affected220 at risk
Malaise	General disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Multiple organ dysfunction syndrome	General disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Erysipelas	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0013 affected220 at risk
Diarrhoea infectious	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Encephalitis	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Infection	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0011 affected220 at risk
Ischaemic stroke	Nervous system disorders	MedDRA v23.1	Non-systematic Assessment	EG0002 affected216 at risk EG0013 affected220 at risk
Seizure	Nervous system disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0011 affected220 at risk
Syncope	Nervous system disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0012 affected220 at risk
Autoimmune encephalopathy	Nervous system disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Encephalitis autoimmune	Nervous system disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Leukoencephalopathy	Nervous system disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Presyncope	Nervous system disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0005 affected216 at risk EG0013 affected220 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Blood bilirubin increased	Investigations	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0012 affected220 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0012 affected220 at risk
Blood creatinine increased	Investigations	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0012 affected220 at risk
Aspartate aminotransferase increased	Investigations	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0012 affected220 at risk
Alanine aminotransferase increased	Investigations	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
General physical condition abnormal	Investigations	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Transaminases increased	Investigations	MedDRA v23.1	Non-systematic Assessment	EG0002 affected216 at risk EG0010 affected220 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0014 affected220 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0013 affected220 at risk
Dermatitis	Skin and subcutaneous tissue disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Dermatitis allergic	Skin and subcutaneous tissue disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Dermatitis exfoliative generalised	Skin and subcutaneous tissue disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Pemphigoid	Skin and subcutaneous tissue disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Rash macular	Skin and subcutaneous tissue disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Atrial fibrillation	Cardiac disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0013 affected220 at risk
Atrial flutter	Cardiac disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0011 affected220 at risk
Angina pectoris	Cardiac disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Cardiac failure acute	Cardiac disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Myocarditis	Cardiac disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0012 affected220 at risk
Tachyarrhythmia	Cardiac disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Rhabdomyolysis	Musculoskeletal and connective tissue disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0014 affected220 at risk
Muscular weakness	Musculoskeletal and connective tissue disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Myositis	Musculoskeletal and connective tissue disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0011 affected220 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Hyponatraemia	Metabolism and nutrition disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0011 affected220 at risk
Hypovolaemia	Metabolism and nutrition disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Renal failure	Renal and urinary disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0013 affected220 at risk
Acute kidney injury	Renal and urinary disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0012 affected220 at risk
Infusion related reaction	Injury, poisoning and procedural complications	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0013 affected220 at risk
Hypotension	Vascular disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Anaemia	Blood and lymphatic system disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0012 affected220 at risk
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Chorioretinopathy	Eye disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0012 affected220 at risk
Visual impairment	Eye disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Hepatic failure	Hepatobiliary disorders	MedDRA v23.1	Non-systematic Assessment	EG0002 affected216 at risk EG0010 affected220 at risk
Hepatitis	Hepatobiliary disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Adrenal insufficiency	Endocrine disorders	MedDRA v23.1	Non-systematic Assessment	EG0002 affected216 at risk EG0010 affected220 at risk
Hypersensitivity	Immune system disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0002 affected216 at risk EG0013 affected220 at risk
Autoimmune hepatitis	Hepatobiliary disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0011 affected220 at risk
Cardiac failure	Cardiac disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0012 affected220 at risk
Accidental overdose	Injury, poisoning and procedural complications	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Cholestasis	Hepatobiliary disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Immune-mediated neuropathy	Nervous system disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Autoimmune nephritis	Renal and urinary disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Gastritis	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Gastroenteritis	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Lipase increased	Investigations	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Urinary tract infection	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0012 affected220 at risk
Sepsis	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0016 affected220 at risk
Pneumonia	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0013 affected220 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0012 affected220 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0002 affected216 at risk EG0011 affected220 at risk
Respiratory tract infection	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0011 affected220 at risk
Urosepsis	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0012 affected220 at risk
Ankle fracture	Injury, poisoning and procedural complications	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Appendicitis	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Ascites	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Basal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Bladder perforation	Renal and urinary disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Bradycardia	Cardiac disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Brain oedema	Nervous system disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
COVID-19 pneumonia	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Cardiac tamponade	Cardiac disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Cellulitis	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Chest pain	General disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Dacryocystitis	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Device related infection	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Device related sepsis	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Diplopia	Eye disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Dupuytren's contracture	Musculoskeletal and connective tissue disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Dyskinesia	Nervous system disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Endocarditis	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Fall	Injury, poisoning and procedural complications	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Femur fracture	Injury, poisoning and procedural complications	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Gastric ulcer	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Gastrointestinal obstruction	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Haematochezia	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Haematoma	Vascular disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Haematuria	Renal and urinary disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Headache	Nervous system disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Hepatic cirrhosis	Hepatobiliary disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Hepatic pain	Hepatobiliary disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Hip fracture	Injury, poisoning and procedural complications	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Hypertension	Vascular disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Hypoglycaemia	Metabolism and nutrition disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Hypotensive crisis	Vascular disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Hysterectomy	Surgical and medical procedures	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Influenza	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Interstitial lung disease	Respiratory, thoracic and mediastinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Intestinal obstruction	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Intracranial pressure increased	Nervous system disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Lower respiratory tract infection	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Nervous system disorder	Nervous system disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Non-cardiac chest pain	General disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Orthostatic hypotension	Vascular disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Pneumonia viral	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Radiculopathy	Nervous system disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Rectal haemorrhage	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Scleroderma	Musculoskeletal and connective tissue disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Sinusitis	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Spinal pain	Musculoskeletal and connective tissue disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Spleen tuberculosis	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Subileus	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Superinfection viral	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Thrombosis mesenteric vessel	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Tonsilitis	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Toxic shock syndrome	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk
Transient ischaemic attack	Nervous system disorders	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Tumour haemorrhage	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Tumour pain	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Upper limb fracture	Injury, poisoning and procedural complications	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0001 affected216 at risk EG0010 affected220 at risk
Wound infection	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0000 affected216 at risk EG0011 affected220 at risk

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA v23.1	Non-systematic Assessment	EG00018 events17 affected216 at risk EG00150 events32 affected220 at risk
Hyperthyroidism	Endocrine disorders	MedDRA v23.1	Non-systematic Assessment	EG00022 events21 affected216 at risk EG00110 events10 affected220 at risk
Hypothyroidism	Endocrine disorders	MedDRA v23.1	Non-systematic Assessment	EG00017 events17 affected216 at risk EG00117 events15 affected220 at risk
Abdominal pain	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG00022 events18 affected216 at risk EG00129 events24 affected220 at risk
Constipation	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG00026 events20 affected216 at risk EG00136 events32 affected220 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG00058 events42 affected216 at risk EG001293 events120 affected220 at risk
Dry mouth	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0009 events9 affected216 at risk EG00119 events18 affected220 at risk
Nausea	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG00032 events28 affected216 at risk EG00161 events54 affected220 at risk
Stomatitis	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG0004 events3 affected216 at risk EG00119 events14 affected220 at risk
Vomiting	Gastrointestinal disorders	MedDRA v23.1	Non-systematic Assessment	EG00016 events15 affected216 at risk EG00153 events41 affected220 at risk
Asthenia	General disorders	MedDRA v23.1	Non-systematic Assessment	EG00049 events42 affected216 at risk EG00189 events59 affected220 at risk
Fatigue	General disorders	MedDRA v23.1	Non-systematic Assessment	EG00054 events42 affected216 at risk EG00164 events43 affected220 at risk
Oedema peripheral	General disorders	MedDRA v23.1	Non-systematic Assessment	EG00020 events17 affected216 at risk EG00176 events50 affected220 at risk
Pyrexia	General disorders	MedDRA v23.1	Non-systematic Assessment	EG00019 events17 affected216 at risk EG00187 events65 affected220 at risk
Folliculitis	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0002 events2 affected216 at risk EG00124 events15 affected220 at risk
Rash pustular	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0002 events2 affected216 at risk EG00112 events11 affected220 at risk
Urinary tract infection	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0004 events4 affected216 at risk EG00118 events13 affected220 at risk
Alanine aminotransferase increased	Investigations	MedDRA v23.1	Non-systematic Assessment	EG00019 events18 affected216 at risk EG00142 events30 affected220 at risk
Amylase increased	Investigations	MedDRA v23.1	Non-systematic Assessment	EG00010 events9 affected216 at risk EG00129 events19 affected220 at risk
Aspartate aminotransferase increased	Investigations	MedDRA v23.1	Non-systematic Assessment	EG00020 events18 affected216 at risk EG00157 events42 affected220 at risk
Blood creatine phosphokinase increased	Investigations	MedDRA v23.1	Non-systematic Assessment	EG00016 events13 affected216 at risk EG001127 events81 affected220 at risk
Blood lactate dehydrogenase increased	Investigations	MedDRA v23.1	Non-systematic Assessment	EG0005 events5 affected216 at risk EG00119 events15 affected220 at risk
Lipase increased	Investigations	MedDRA v23.1	Non-systematic Assessment	EG00018 events15 affected216 at risk EG00151 events28 affected220 at risk
Decreased appetite	Metabolism and nutrition disorders	MedDRA v23.1	Non-systematic Assessment	EG00018 events16 affected216 at risk EG00135 events30 affected220 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA v23.1	Non-systematic Assessment	EG00013 events11 affected216 at risk EG00123 events19 affected220 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	MedDRA v23.1	Non-systematic Assessment	EG00048 events37 affected216 at risk EG00123 events21 affected220 at risk
Back pain	Musculoskeletal and connective tissue disorders	MedDRA v23.1	Non-systematic Assessment	EG00029 events19 affected216 at risk EG00117 events12 affected220 at risk
Myalgia	Musculoskeletal and connective tissue disorders	MedDRA v23.1	Non-systematic Assessment	EG00012 events12 affected216 at risk EG00120 events18 affected220 at risk
Pain in extremity	Musculoskeletal and connective tissue disorders	MedDRA v23.1	Non-systematic Assessment	EG0009 events8 affected216 at risk EG00112 events11 affected220 at risk
Dizziness	Nervous system disorders	MedDRA v23.1	Non-systematic Assessment	EG00011 events8 affected216 at risk EG00123 events18 affected220 at risk
Headache	Nervous system disorders	MedDRA v23.1	Non-systematic Assessment	EG00019 events17 affected216 at risk EG00136 events30 affected220 at risk
Cough	Respiratory, thoracic and mediastinal disorders	MedDRA v23.1	Non-systematic Assessment	EG00027 events23 affected216 at risk EG00126 events21 affected220 at risk
Dyspnoea	Respiratory, thoracic and mediastinal disorders	MedDRA v23.1	Non-systematic Assessment	EG00020 events19 affected216 at risk EG00124 events18 affected220 at risk
Dermatitis acneiform	Skin and subcutaneous tissue disorders	MedDRA v23.1	Non-systematic Assessment	EG0003 events3 affected216 at risk EG00168 events50 affected220 at risk
Dry skin	Skin and subcutaneous tissue disorders	MedDRA v23.1	Non-systematic Assessment	EG00015 events14 affected216 at risk EG00121 events15 affected220 at risk
Erythema	Skin and subcutaneous tissue disorders	MedDRA v23.1	Non-systematic Assessment	EG00012 events9 affected216 at risk EG00120 events16 affected220 at risk
Pruritis	Skin and subcutaneous tissue disorders	MedDRA v23.1	Non-systematic Assessment	EG00042 events35 affected216 at risk EG00164 events44 affected220 at risk
Rash	Skin and subcutaneous tissue disorders	MedDRA v23.1	Non-systematic Assessment	EG00037 events27 affected216 at risk EG001154 events90 affected220 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	MedDRA v23.1	Non-systematic Assessment	EG0007 events5 affected216 at risk EG00139 events26 affected220 at risk
Hypertension	Vascular disorders	MedDRA v23.1	Non-systematic Assessment	EG00021 events15 affected216 at risk EG00129 events24 affected220 at risk
Nasopharyngitis	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG00015 events10 affected216 at risk EG00113 events12 affected220 at risk
Paronychia	Infections and infestations	MedDRA v23.1	Non-systematic Assessment	EG0001 events1 affected216 at risk EG00114 events13 affected220 at risk
Weight decreased	Investigations	MedDRA v23.1	Non-systematic Assessment	EG00013 events12 affected216 at risk EG00113 events11 affected220 at risk
Paraesthesia	Nervous system disorders	MedDRA v23.1	Non-systematic Assessment	EG0006 events6 affected216 at risk EG00112 events11 affected220 at risk
Vitiligo	Skin and subcutaneous tissue disorders	MedDRA v23.1	Non-systematic Assessment	EG00020 events19 affected216 at risk EG0016 events6 affected220 at risk

ID	Title	Description
BG000	Pembrolizumab	Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.
BG001	Cobimetinib and Atezolizumab	Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.
BG002	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pembrolizumab	Participants received 200 mg of intravenous (IV) pembrolizumab every 3 weeks (Q3W) until investigator-determined disease progression, unacceptable toxicity, death, patient or physician decision to withdraw, or pregnancy, whichever occurred first.	68	224	56	216	173	216
EG001	Cobimetinib and Atezolizumab	Participants received 60 mg of cobimetinib by mouth (PO) on a 21 days on, 7 days off schedule (dosing on Days 1-21, followed by no dosing on Days 22-28) plus 840 mg of atezolizumab by IV infusion of Days 1 and 15 of each 28-day cycle.	70	222	105	220	209	220

ID	Term
C574276	cobimetinib
C000594389	atezolizumab
C582435	pembrolizumab