A Study of Cobimetinib Plus Atezolizumab Versus Pembrolizumab in Participants With Previously Untreated Advanced BRAFv600 Wild-Type Melanoma
Advanced BRAFV600 Wild-type Melanoma

About this trial
This is an interventional treatment trial for Advanced BRAFV600 Wild-type Melanoma
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
Sites / Locations
- University of Arizona Cancer Center
- City of Hope Comprehensive Cancer Center
- USC Norris Cancer Center
- USC Norris Cancer Center; USC Oncology Hematology Newport Beach
- University of California at Irvine Medical Center; Department of Oncology
- Stanford Comprehensive Cancer Center
- UF Health Cancer Center at Orlando Health
- Florida Cancer Specialist, North Region
- Moffitt Cancer Center
- Florida Cancer Specialists
- Northwestern University
- Massachusetts General Hospital;Hematology/ Oncology
- University of Michigan; Michigan Institute for Clinical and Health Research (MICHR)
- Dartmouth-Hitchcock Medical Center; Hematology/Oncology
- Morristown Medical Center
- Forsythe Memorial Hospital Inc., dba Novant Health Oncology Specialists
- TriHealth Hatton Institute; Surgical Education
- St. Luke's University Health network
- Thomas Jefferson University Hospital;Medical Oncology
- SCRI Tennessee Oncology Chattanooga
- Sarah Cannon Research Institute
- M.D Anderson Cancer Center; Uni of Texas At Houston
- West Virginia University Hospitals Inc
- Cairns Base Hospital
- Townsville General Hospital
- Princess Alexandra Hospital
- Royal Hobart Hospital
- Fiona Stanley Hospital
- Cliniques Universitaires St-Luc
- AZ Groeninge
- UZ Leuven Gasthuisberg
- Instituto Nacional de Cancer - INCa; Oncologia
- Hospital das Clinicas - UFRGS
- Hopital Avicenne; Dermatologie
- Hopital Saint Andre CHU De Bordeaux; Dermatologie
- Chu Site Du Bocage;Dermatologie
- CHU de Grenoble - Hôpital Nord
- Centre Hospitalier Le Mans; Dermatologie
- Hopital Claude Huriez; Sce Dermatologie
- Hopital Timone Adultes; Dermatologie
- CHU de Nantes; Cancéro-dermatologie
- Hopital l Archet 2; Ginestriere, Service de; Dermatologie
- Groupe Hospitalier Bichat Claude Bernard
- Hopital Saint Louis; Dermatologie 1
- Hopital Robert Debre; DERMATOLOGIE
- Centre Eugene Marquis; Service d'oncologie
- Hopital Charles Nicolle; Dermatologie Serv.
- Institut Universitaire du Cancer - Oncopole Toulouse (IUCT-O)
- Institut Gustave Roussy; Dermatologie
- Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik für Dermatologie
- HELIOS Klinikum Erfurt; Klinik für Dermatologie & Allergologie
- Universitatsklinikum Essen; Klinik für Dermatologie
- Klinik Johann Wolfgang von Goethe Uni; Klinik für Dermatologie, Venerologie und Allergologie
- SRH Wald-Klinikum Gera; Klinik für Hautkrankheiten und Allergologie
- Medizinische Hochschule Hannover; Klinik für Dermatologie, Allergologie und Venerologie
- UKSH Kiel; Klinik für Dermatologie, Venerologie und Allergologie
- Universitatsklinikum Mainz; Klinik und Poliklinik fur Dermatologie
- Klinikum Mannheim Klinik fuer Dermatologie, Venerologie und Allergologie
- Johannes Wesling Klinikum Minden; Hämatologie, Onkologie, Hämostaseologie und Palliativmedizin
- Klinikum der Ludwigs-Maximilians-Universität München; Dermatologie
- Fachklinik Hornheide; Dermatologie
- Zentrum für Dermatoonkologie, Universitäts-Hautklinik Tübingen
- Anticancer Hospital Ag. Savas ; 2Nd Dept. of Oncology - Internal Medicine
- Laiko General Hospital Athen
- Metropolitan Hospital; Dept. of Oncology
- Bioclinic Thessaloniki
- Orszagos Onkologiai Intezet; Borgyogyaszati Osztaly
- Pecsi Tudomanyegyetem AOK; Borgyogyaszati Klinika
- University of Szeged Szent-Györgyi Albert Clinical Center; Department of Dermatology and Allergology
- Azienda Osp Uni Seconda Università Degli Studi Di Napoli; Unità Operativa Oncologia Medica
- IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica B
- A.O. Universitaria Policlinico Di Modena; Ematologia
- IFO - Istituto Regina Elena; Oncologia Medica
- IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A
- Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2
- Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica
- Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico
- A.O.U. Cons. Policlinico Bari - Consorzlale Policlinico; Scienze Biomediche e Oncologia Umana
- Azienda Ospedaliero - Universitaria Pisana U.O. Oncologia Medica 2 Universitaria - Polo Oncologico
- IOV - Istituto Oncologico Veneto IRCCS
- Seoul National University Hospital
- Severance Hospital, Yonsei University Health System
- Asan Medical Center
- Samsung Medical Center
- Antoni Van Leeuwenhoek Ziekenhuis; Inwendige Geneeskunde
- Amphia Ziekenhuis, locatie Langendijk;Oncology
- Erasmus Mc - Daniel Den Hoed Kliniek; Interne Oncologie
- Zuyderland ziekenhuis locatie Geleen
- Copernicus Podmiot Medyczny Sp. z o.o. Wojewodzkie Centrum Onkologii
- COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej
- Szpital Kliniczny im. Heliodora Święcickiego UM w Poznaniu.
- Zachodniopomorskie Centrum Onkologii, Osrodek Innowacyjnosci, Rozwoju i Badan Klinicznych
- Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
- Dolnośląskie Centrum Onkologii, Pulmonologii i Hematologii
- Moscow City Oncology Hospital #62
- FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"
- FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"
- St. Petersburg Oncology Hospital
- Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
- Hospital Universitario Son Espases; Servicio de Oncologia
- Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia
- Hospital Universitario Materno Infantil de Gran Canaria; Servicio de Oncologia
- Clinica Universitaria de Navarra; Servicio de oncología
- Hospital Univ Vall d'Hebron; Servicio de Oncologia
- Hospital Clínic i Provincial; Servicio de Oncología
- Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
- Hospital Ramon y Cajal; Servicio de Oncologia
- Hospital Universitario 12 de Octubre; Servicio de Oncologia
- Hospital Universitario La Paz; Servicio de Oncologia
- Hospital Universitario Virgen Macarena; Servicio de Oncologia
- Instituto Valenciano Oncologia; Oncologia Medica
- Hospital General Universitario de Valencia; Servicio de oncologia
- Hospital Universitario Miguel Servet; Servicio Oncologia
- BRISTOL ONCOLOGY CENTRE; CLINICAL TRIALS UNIT; R & D department
- Western General Hospital; Edinburgh Cancer Center
- Leicester Royal Infirmary; Dept. of Medical Oncology
- University College London Hospital
- Guys & St Thomas Hospital; Department of Oncology
- University Hospitals of North Midlands NHS Trust-Royal Stoke University Hospital
- Singleton Hospital; Pharmacy
- Royal Cornwall Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
Cobimetinib and Atezolizumab
Pembrolizumab
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.
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.