A Study of Atezolizumab Plus Cobimetinib and Vemurafenib Versus Placebo Plus Cobimetinib and Vemurafenib in Previously Untreated BRAFv600 Mutation-Positive Patients With Metastatic or Unresectable Locally Advanced Melanoma

A Phase III, Double-Blinded, Randomized, Placebo-Controlled Study of Atezolizumab Plus Cobimetinib and Vemurafenib Versus Placebo Plus Cobimetinib and Vemurafenib in Previously Untreated BRAFV600 Mutation-Positive Patients With Unresectable Locally Advanced or Metastatic Melanoma

This is a Phase III, double-blinded, placebo-controlled, randomized, multicenter study designed to evaluate the efficacy, safety, and pharmacokinetics of atezolizumab + cobimetinib + vemurafenib compared with placebo + cobimetinib + vemurafenib in patients with previously untreated BRAFv600 mutation-positive metastatic or unresectable locally advanced melanoma.

Study Overview

• Status: Completed
• Conditions: Melanoma
• Intervention / Treatment: Drug: Atezolizumab; Drug: Cobimetinib; Drug: Vemurafenib; Drug: Vemurafenib Placebo; Drug: Atezolizumab Placebo

• Study Type: Interventional
• Enrollment (Actual): 514
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • Woolloongabba, Queensland, Australia, 4102
      • Princess Alexandra Hospital
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Centre
  • Western Australia
    • Murdoch, Western Australia, Australia, 6150
      • Fiona Stanley Hospital
• Austria
  • Graz, Austria, 8030
    • Medical University of Graz, Department of Dermatology
  • Innsbruck, Austria, 6020
    • LKH Innsbruck
  • Wien, Austria, 1090
    • Medizinische Universität Wien
• Belgium
  • Bruxelles, Belgium, 1200
    • Cliniques Universitaires St-Luc
  • Leuven, Belgium, 3000
    • UZ Leuven Gasthuisberg
  • Liège, Belgium, 4000
    • CHU Sart-Tilman
  • Wilrijk, Belgium, 2610
    • Sint Augustinus Wilrijk
• Brazil
  • Rio De Janeiro, Brazil, 22290-160
    • Clinicas Oncologicas Integradas - COI
  • São Paulo, Brazil, 01321-00
    • Beneficencia Portuguesa de Sao Paulo
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-003
      • Hospital das Clinicas - UFRGS
  • Santa Catarina
    • Florianopolis, Santa Catarina, Brazil, 88020-210
      • Centro de Pesquisa e Ensino em Oncologia de Santa Catarina - CEPEN
  • São Paulo
    • Sao Paulo, São Paulo, Brazil, 01246-000
      • Instituto do Câncer do Estado de São Paulo - ICESP
• Canada
  • Quebec, Canada, G1J 1Z4
    • CHU de Quebec - Hopital de l'Enfant-Jesus
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Arthur J.E. Child Comprehensive Cancer Center-Calgary
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • Cancer Care Manitoba
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Juravinski Cancer Clinic
    • London, Ontario, Canada, N6A 4L6
      • LHSC - Victoria Hospital
    • Oshawa, Ontario, Canada, L1G 2B9
      • Lakeridge Health Oshawa
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital Cancer Centre
    • Toronto, Ontario, Canada, M4X 1K9
      • Princess Margaret Hospital
• France
  • Bordeaux, France, 33075
    • Groupe Hospitalier Saint André - Hôpital Saint André
  • Grenoble, France, 38043
    • Centre Hospitalier Universitaire de Grenoble - Albert Michallon
  • Lille, France, 59037
    • Hopital Claude Huriez - CHU Lille
  • Nantes, France, 44093
    • CHU de Nantes
  • Reims, France, 51092
    • Hopital Robert Debre
  • Rennes, France, 35042
    • Centre Eugène Marquis
  • Rouen, France, 76031
    • CHU de Rouen - Hôpital Charles Nicolle
• Germany
  • Berlin, Germany, 10117
    • Charité - Universitätsmedizin Berlin
  • Buxtehude, Germany, 21616
    • Elbekliniken Buxtehude
  • Erfurt, Germany, 99089
    • Helios Klinikum Erfurt
  • Essen, Germany, 45147
    • Universitätsklinikum Essen
  • Göttingen, Germany, 37075
    • Universitatsmedizin Gottingen
  • Hannover, Germany, 30625
    • Medizinische Hochschule Hannover
  • Heidelberg, Germany, 69120
    • Universitätsklinik Heidelberg
  • Kiel, Germany, 24105
    • UKSH Kiel
  • Köln, Germany, 50937
    • Klinikum d.Universität zu Köln Klinik u.Poliklinik f.Dermatologie
  • Leipzig, Germany, 04103
    • Universitatsklinikum Leipzig
  • Lübeck, Germany, 23538
    • UKSH Universitatsklinikum Schleswig-Holstein
  • Mainz, Germany, 55131
    • Universitätsklinikum Mainz
  • München, Germany, 80337
    • Klinikum der Ludwigs-Maximilians-Universität München
  • Münster, Germany, 48157
    • Fachklinik Hornheide
  • Quedlinburg, Germany, 06484
    • Harzklinikum Dorothea Christiane Erxleben GmbH, Standort Quedlinburg
  • Regensburg, Germany, 93053
    • Universitätsklinikum Regensburg
  • Tübingen, Germany, 72076
    • Zentrum für Dermatoonkologie, Universitäts-Hautklinik Tübingen
  • Würzburg, Germany, 97080
    • Universitätsklinikum Würzburg
• Greece
  • Athens, Greece, 115 27
    • Laiko General Hospital Athen
  • Pireaus, Greece, 185 47
    • Metropolitan Hospital
• Hungary
  • Budapest, Hungary, 1122
    • Orszagos Onkologiai Intezet
  • Szeged, Hungary, 6720
    • University of Szeged Szent-Györgyi Albert Clinical Center
• Israel
  • Haifa, Israel, 3109601
    • Rambam Health Care Campus
  • Jerusalem, Israel, 12000
    • Sharett Institute - Hadassah Hebrew University Medical Center
  • Petach Tikva, Israel, 4941492
    • Rabin MC
  • Ramat-Gan, Israel, 5265601
    • Ella Institute - Sheba Medical Center
• Italy
  • Campania
    • Napoli, Campania, Italy, 80131
      • Irccs Istituto Nazionale Tumori Fondazione Pascale
  • Emilia-Romagna
    • Meldola, Emilia-Romagna, Italy, 47014
      • IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola
  • Friuli-Venezia Giulia
    • Udine, Friuli-Venezia Giulia, Italy, 33100
      • A.O. Universitaria S. Maria Della Misericordia Di Udine
  • Lazio
    • Roma, Lazio, Italy, 00168
      • IFO - Istituto Regina Elena
  • Liguria
    • Genova, Liguria, Italy, 16132
      • IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST)
  • Lombardia
    • Milano, Lombardia, Italy, 20141
      • Irccs Istituto Europeo di Oncologia (IEO)
    • Milano, Lombardia, Italy, 20133
      • Irccs Istituto Nazionale Dei Tumori (Int)
  • Piemonte
    • Candiolo, Piemonte, Italy, 10060
      • Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo
  • Puglia
    • Bari, Puglia, Italy, 70124
      • Istituto Tumori ?Giovanni Paolo II?, Oncologia
  • Toscana
    • Siena, Toscana, Italy, 53100
      • A.O.U. Senese Policlinico Santa Maria alle Scotte
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
• Netherlands
  • Rotterdam, Netherlands, 3075 EA
    • Erasmus Mc - Daniel Den Hoed Kliniek
• New Zealand
  • Newtown, Wellington, New Zealand, 6021
    • Wellington Hospital
  • Palmerston North, New Zealand, 4442
    • Mid Central DHB
  • Tauranga, New Zealand, 3112
    • Tauranga Hospital, Clinical Trials Unit
• Poland
  • Gdansk, Poland, 80-952
    • Uniwersyteckie Centrum Kliniczne
  • Kraków, Poland, 31-115
    • Narodowy Inst.Onkol.im.Sk?odowskiej-Curie Pa?stw.Inst.Badawczy Kraków
  • Lublin, Poland, 20-090
    • COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej
  • Pozna?, Poland, 60-355
    • Uniwersytecki Szpital Kliniczny W Poznaniu
  • Warszawa, Poland, 02-781
    • Narodowy Instytut Onkologii im. Marii Sk?odowskiej-Curie - Pa?stwowy Instytut Badawczy
  • Wroclaw, Poland, 53-413
    • Dolno?L?Skie Centrum Onkologii, Pulmonologii I Hematologii
• Portugal
  • Lisboa, Portugal, 1099-023
    • IPO de Lisboa
  • Porto, Portugal, 4200-072
    • IPO do Porto
• Russian Federation
  • Moskovskaja Oblast
    • Moscovskaya Oblast, Moskovskaja Oblast, Russian Federation, 143423
      • Moscow City Oncology Hospital #62
    • Moscow, Moskovskaja Oblast, Russian Federation, 115478
      • FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"
  • Sankt Petersburg
    • Saint-Petersburg, Sankt Petersburg, Russian Federation, DUMMY_VALUE
      • FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Barcelona, Spain, 08036
    • Hospital Clinic I Provincial
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28034
    • Hospital Ramon y Cajal
  • Sevilla, Spain, 41071
    • Hospital Universitario Virgen De La Macarena
  • Valencia, Spain, 46014
    • Hospital General Universitario de Valencia
  • Valencia, Spain, 04600
    • Fundacion Instituto Valenciano de Oncologia (IVO)
  • Zaragoza, Spain, 50009
    • Hospital Universitario Miguel Servet
  • Navarra
    • Pamplona, Navarra, Spain, 31008
      • Clinica Universitaria De Navarra
• United Kingdom
  • Bristol, United Kingdom, BS2 8ED
    • Bristol Haematology and Oncology Centre
  • Glasgow, United Kingdom, G12 0YN
    • Beatson West of Scotland Cancer Centre
  • Ipswich, United Kingdom, IP4 5PD
    • Ipswich Hospital
  • Leeds, United Kingdom, LS9 7TF
    • St James Uni Hospital
  • London, United Kingdom, SE1 9RT
    • Guys and St Thomas NHS Foundation Trust, Guys Hospital
  • New Castle Upon Tyne, United Kingdom, NE7 7DN
    • Freeman Hospital
  • Swansea, United Kingdom, SA2 8QA
    • Singleton Hospital
  • Truro, United Kingdom, TR1 3LJ
    • Royal Cornwall Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294-3300
      • University of Alabama at Birmingham
  • Arizona
    • Tempe, Arizona, United States, 85284
      • Arizona Oncology Associates, PC - HAL
  • Arkansas
    • Springdale, Arkansas, United States, 72762
      • Highlands Oncology Group
  • California
    • Orange, California, United States, 92868
      • UC Irvine Medical Center
  • Florida
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Medical Center
    • Orlando, Florida, United States, 32806
      • UF Health Cancer Center at Orlando Health
  • Pennsylvania
    • Bethlehem, Pennsylvania, United States, 18015
      • St. Luke's University Health Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Females of child bearing potential and males with female partners must and use of contraceptive methods with a failure rate of less than or equal to (</=)1% per year is required during treatment and for 6 months post treatment. Males should not expose pregnant partners to sperm and refrain from donating sperm for 6 months post treatment. Women must refrain from donating eggs during this same period
• Histologically confirmed Stage IV (metastatic) or unresectable Stage IIIc (locally advanced) melanoma
• Naive to prior systemic anti-cancer therapy for melanoma (example: chemotherapy, hormonal therapy, targeted therapy, immunotherapy, or other biologic therapies) except adjuvant treatment with interferon (IFN), interleukin (IL)-2, or vaccine therapies or herbal therapies
• Documentation of BRAFv600 mutation-positive status in melanoma tumor tissue (archival or newly obtained) through use of a clinical mutation test approved by the local health authority
• Eastern Cooperative Oncology Group Performance (ECOG) Status of 0 or 1
• Measurable disease according to RECIST v1.1 (must be outside central nervous system (CNS))
• Life expectancy >/=18 weeks
• For participants not receiving therapeutic anticoagulation: International normalized ratio (INR) or activated partial thromboplastin time (aPTT) less than or equal to (</=) 1.5*upper limit of normal (ULN) within 28 days prior to initiation of study treatment
• For participants receiving therapeutic anticoagulation: stable anticoagulant regimen and stable INR during the 28 days immediately preceding initiation of study treatment

Exclusion Criteria:

Cancer-Related Exclusion Criteria:

• Major surgical procedure within 4 weeks prior study treatment initiation
• Traumatic injury or palliative radiotherapy within 2 weeks prior study treatment initiation
• Active malignancy (other than BRAFv600 mutation-positive melanoma) or malignancy within 3 years prior to screening are excluded, with the exception of resected melanoma, resected basal cell carcinoma (BCC), resected cutaneous squamous cell carcinoma (SCC), resected carcinoma in situ of the cervix, resected carcinoma in situ of the breast, in situ prostate cancer, limited-stage bladder cancer, or any other curatively treated malignancies from which the participant has been disease-free for at least 3 years

Ocular Exclusion Criteria:

• History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioretinopathy, retinal vein occlusion (RVO), or neovascular macular degeneration

Cardiac Exclusion Criteria:

• History of clinically significant cardiac dysfunction
• Left ventricular ejection fraction (LVEF) below the institutional lower limit of normal or below 50%

Central Nervous System (CNS) Exclusion Criteria:

• Untreated or actively progressing CNS lesions (carcinomatous meningitis)
• History of metastases to brain stem, midbrain, pons, or medulla, or within 10 millimeter (mm) of the optic apparatus (optic nerves and chiasm); or leptomeningeal metastatic disease; or intracranial hemorrhage

Additional Exclusion Criteria:

• Uncontrolled diabetes or symptomatic hyperglycemia
• Current severe, uncontrolled systemic disease (including, but not limited to, clinically significant cardiovascular, pulmonary, or renal disease) other than cancer
• History of malabsorption or other clinically significant metabolic dysfunction
• Pregnant or breastfeeding, or intending to become pregnant during the study
• Prior allogeneic stem cell or solid organ transplantation
• History of idiopathic pulmonary fibrosis, organizing pneumonia (example: bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• Active or history of autoimmune disease or immune deficiency
• Known clinically significant liver disease, inherited liver disease and active viral disease
• Active tuberculosis
• Treatment with therapeutic oral or intravenous (IV) antibiotics; or with a live, attenuated vaccine; or systemic immunosuppressive medication
• Known hypersensitivity to biopharmaceutical agents produced in Chinese hamster ovary cells or any component of the atezolizumab, cobimetinib, or vemurafenib formulations
• Any grade >/=3 hemorrhage or bleeding event within 4 weeks prior to initiation of study treatment
• History of stroke, reversible ischemic neurological defect, or transient ischemic attack within 6 months prior to initiation of study treatment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atezolizumab + Cobimetinib + Vemurafenib + Vemurafenib Placebo; Run-In Period (Cycle 1=28 days): Participants will receive vemurafenib 960 mg (four, 240 mg tablets) PO BID along with cobimetinib 60 mg (three, 20 mg tablets) PO QD on Days 1 to 21 followed by vemurafenib 720 mg (three, 240 mg tablets) PO BID on Days 22 to 28 and vemurafenib placebo (1 tablet) PO BID on Days 22 to 28. Triple Combination Period (Cycle 1 onwards): Participants will receive atezolizumab 840 mg IV infusion on Day 1 and 15, cobimetinib 60 mg (three, 20 mg tablets) PO QD on Days 1 to 21, vemurafenib 720 mg (three, 240 mg tablets) PO BID on Days 1 to 28, and vemurafenib placebo (1 tablet) PO BID on Days 1 to 28 of each 28-day cycle. Study treatment will continue until investigator-determined disease progression, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurs first.	Drug: Atezolizumab; Will be administered as per the schedule described in individual arm.; Drug: Cobimetinib; Will be administered as per the schedule described in individual arm.; Drug: Vemurafenib; Will be administered as per the schedule described in individual arm.; Drug: Vemurafenib Placebo; Will be administered as per the schedule described in individual arm.
Experimental: Atezolizumab Placebo + Cobimetinib + Vemurafenib; Run-In Period (Cycle1=28 days): Participants will receive vemurafenib 960 milligrams (mg) (four, 240 mg tablets) orally (PO) twice a day (BID) along with cobimetinib 60 mg (three, 20 mg tablets) PO once a day (QD) on Days 1 to 21 followed by vemurafenib 960 mg (four, 240 mg tablets) PO BID on Days 22 to 28. Triple Combination Period (Cycle 1 onwards): Participants will receive ATZ placebo by intravenous (IV) infusion on Day 1 and 15, cobimetinib 60 mg (three, 20 mg tablets) PO QD on Days 1 to 21, and vemurafenib 960 mg (four, 240 mg tablets) PO BID on Days 1 to 28 of each 28-day cycle. Study treatment will continue until investigator-determined disease progression, death, unacceptable toxicity, withdrawal of consent, or pregnancy, whichever occurs first.	Drug: Cobimetinib; Will be administered as per the schedule described in individual arm.; Drug: Vemurafenib; Will be administered as per the schedule described in individual arm.; Drug: Atezolizumab Placebo; Will be administered as per the schedule described in individual arm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS), as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1	PFS was defined as the time from randomization to the first occurrence of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the sum of diameters (SOD) of target lesions, taking as reference smallest sum on study, including baseline. In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of at least 5 millimeters (mm).	Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 33 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS as Determined by Independent Review Committee (IRC) Using RECIST v1.1	PFS was defined as the time from randomization to the first occurrence of disease progression, as determined by the IRC according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference smallest sum on study, including baseline. In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of at least 5 mm.	Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 33 months)
Percentage of Participants With Objective Response (OR), as Determined by Investigator Using RECIST V1.1	OR rate was defined as percentage of participants with partial response (PR) or complete response (CR) on 2 consecutive occasions ≥ 4 weeks apart as determined by the investigator using RECIST v.1.1. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD.	Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 56 months)
Duration of Response (DOR), as Determined by Investigator Using RECIST v1.1	DOR was defined as the time from the first occurrence of a documented OR to PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurred first. PD was defined as at least a 20% increase in the SOD of target lesions, taking as reference smallest sum on study, including baseline. In addition to the relative increase of 20%, the SOD must also demonstrate an absolute increase of at least 5 mm. CR was defined as the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD.	Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 56 months)
Overall Survival (OS)	OS was defined as the time from randomization to death from any cause.	Baseline up to death due to any cause (up to approximately 85 months)
Percentage of Participants Who Have Survived at 2 Years	Percentage of participants with OS which was defined as the time from randomization to death from any cause. The Kaplan-Meier approach was used to estimate 2-year landmark survival rate. The 95% CI of landmark survival rate was calculated using the standard error derived from Greenwood's formula.	2 years
Time to Deterioration in Global Health Status (GHS) Determined Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Scale Score	Time to deterioration in GHS/health related quality of life (HRQoL) was defined as the time from randomization to first observed ≥ 10-point decrease in EORTC QLQ-C30 linearly transformed GHS/HRQoL scale score that is sustained for two consecutive assessments or followed by death while the participant is on treatment. EORTC QLQ-C30 consists of 30 questions that assess five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The GHS/QoL are scored on a 7-point scale (1=Very Poor to 7=Excellent). The obtained scores are linearly transformed to a score range of 0-100, where higher scores indicate a higher response level and better QoL.	Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 33 months)
Time to Deterioration in Physical Functioning (PF) Determined Using EORTC QLQ-C30 Scale Score	Time to deterioration in PF = time from randomization to first observed ≥ 10-point decrease in EORTC QLQ-C30 linearly transformed PF scale score that is sustained for two consecutive assessments or followed by death while the participant is on treatment. EORTC QLQ-C30 consists of 30 questions that assess 5 aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). PF scale has 5 questions about participant's PF and daily activities (strenuous activities, long walks, short walks, bed/chair rest & needing help with eating, dressing, washing themselves, or using the toilet). PF are scored on a 4-point scale (1=Not at All to 4=Very Much). The obtained scores are linearly transformed to a score range of 0-100, where higher scores indicate a higher response level, functioning/support.	Baseline up to PD or death due to any cause, whichever occurred first (up to approximately 33 months)
Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs)	An AE is any untoward medical occurrence in a participant when administered a pharmaceutical product regardless of the causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom/disease temporally associated with the use of an investigational product, whether or not considered related to the investigational product. A SAE is any significant hazard, contraindication, side effect that is fatal or life-threatening, requires hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is medically significant or requires intervention to prevent one or other of the outcomes listed above. All AEs were reported until 30 days and SAEs until 90 days after the final dose of study treatment or until initiation of subsequent anti-cancer therapy, whichever occurred first.	Up to approximately 85 months
Serum Concentration of Atezolizumab		Pre-infusion Day 1 of Cycles 1-4; 30 minutes post-infusion Day 1 of Cycles 1 and 4; at Atezolizumab discontinuation (up to approximately 33 months) (1 Cycle = 28 days)
Plasma Concentration of Cobimetinib Dose: 20/40 mg		Pre-dose (0 hour) and 3 to 6 hours post dose on Day 15 of Cycles 1 and 4 (1 Cycle = 28 days)
Plasma Concentration of Cobimetinib Dose: 60 mg		Pre-dose (0 hour) and 3 to 6 hours post dose on Day 15 of Cycles 1 and 4 (1 Cycle = 28 days)
Plasma Concentration of Vemurafenib		Pre-dose (0 hour) and 3 to 6 hours post dose on Day 15 of Cycles 1 and 4 (1 Cycle = 28 days)
Percentage of Participants Positive for Anti-drug Antibodies (ADA) to Atezolizumab	Presence of ADAs against atezolizumab during the study relative to the presence of ADAs at baseline. The percentage of ADA-positive participants after drug administration were determined for participants exposed to atezolizumab. For determining post-baseline incidence, participants were considered to be ADA-positive if they were ADA-negative or had missing data at baseline but developed an ADA response following study drug exposure, or if they were ADA-positive at baseline and the titer of 1 or more post-baseline samples was at least 0.60 titer units (t.u.) greater than the baseline titer result.	Pre-infusion Day 1 of Cycles 1-4 (1 Cycle=28 days); at Atezolizumab discontinuation (approximately up to 33 months)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Publications and helpful links

General Publications

• 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.
• Robert C, Lewis KD, Gutzmer R, Stroyakovskiy D, Gogas H, Protsenko S, Pereira RP, Eigentler T, Rutkowski P, Demidov L, Caro I, Forbes H, Shah K, Yan Y, Li H, McArthur GA, Ascierto PA. Biomarkers of treatment benefit with atezolizumab plus vemurafenib plus cobimetinib in BRAFV600 mutation-positive melanoma. Ann Oncol. 2022 May;33(5):544-555. doi: 10.1016/j.annonc.2022.01.076. Epub 2022 Feb 4.
• Gutzmer R, Stroyakovskiy D, Gogas H, Robert C, Lewis K, Protsenko S, Pereira RP, Eigentler T, Rutkowski P, Demidov L, Manikhas GM, Yan Y, Huang KC, Uyei A, McNally V, McArthur GA, Ascierto PA. Atezolizumab, vemurafenib, and cobimetinib as first-line treatment for unresectable advanced BRAFV600 mutation-positive melanoma (IMspire150): primary analysis of the randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2020 Jun 13;395(10240):1835-1844. doi: 10.1016/S0140-6736(20)30934-X.

Study record dates

Study Major Dates

• Study Start (Actual): January 13, 2017
• Primary Completion (Actual): October 11, 2019
• Study Completion (Actual): July 1, 2024

Study Registration Dates

• First Submitted: September 19, 2016
• First Submitted That Met QC Criteria: September 19, 2016
• First Posted (Estimated): September 21, 2016

Study Record Updates

• Last Update Posted (Actual): July 20, 2025
• Last Update Submitted That Met QC Criteria: June 26, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protein Kinase Inhibitors; Atezolizumab; Vemurafenib; Antibodies, Monoclonal
• Other Study ID Numbers: CO39262; 2016-002482-54 (EudraCT Number)