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
Melanoma
About this trial
This is an interventional treatment trial for Melanoma
Eligibility Criteria
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
Sites / Locations
- University of Alabama at Birmingham
- Arizona Oncology Associates, PC - HAL
- Highlands Oncology Group
- UC Irvine Medical Center
- Mount Sinai Medical Center
- UF Health Cancer Center at Orlando Health
- Oncology Specialists, S.C.
- St. Luke's University Health network
- Princess Alexandra Hospital
- Royal Adelaide Hospital
- Peter Maccallum Cancer Centre
- Fiona Stanley Hospital
- Medical University of Graz, Department of Dermatology
- LKH Innsbruck; Universitätsklinik für Dermatologie
- Medizinische Universität Wien; Univ.Klinik für Dermatologie
- Cliniques Universitaires St-Luc
- UZ Leuven Gasthuisberg
- CHU Sart-Tilman
- Sint Augustinus Wilrijk
- Clinicas Oncologicas Integradas - COI
- Hospital das Clinicas - UFRGS
- Centro de Pesquisa e Ensino em Oncologia de Santa Catarina - CEPEN
- Instituto do Cancer do Estado de Sao Paulo - ICESP
- Beneficencia Portuguesa de Sao Paulo
- Tom Baker Cancer Centre-Calgary
- Juravinski Cancer Clinic; Department of Oncology
- LHSC - Victoria Hospital; London Regional Cancer Program
- Lakeridge Health Oshawa; Oncology
- The Ottawa Hospital Cancer Centre; Oncology
- Princess Margaret Hospital
- CHU de Quebec - Hopital de l'Enfant-Jesus; Unite de Recherche en Hematologie et Oncologie
- Groupe Hospitalier Saint André - Hôpital Saint André
- Hopital du Bocage; Dermatologie
- Centre Hospitalier Universitaire de Grenoble - Albert Michallon
- Hopital Claude Huriez - CHU Lille
- Hopital Saint Eloi; CHU de Montpellier; Svc de Dermatologie
- CHU de Nantes; Cancéro-dermatologie
- Hopital Robert Debre; DERMATOLOGIE
- Centre Eugene Marquis; Service d'oncologie
- CHU de Rouen - Hôpital Charles Nicolle
- Institut Gustave Roussy; Dermatologie
- Charite - Universitätsmedizin Berlin
- Elbekliniken Buxtehude; Klinik für Dermatologie
- HELIOS Klinikum Erfurt; Klinik für Dermatologie & Allergologie
- Universitätsklinikum Erlangen; Hautklinik
- Universitatsklinikum Essen; Klinik für Dermatologie
- Universitätsmedizin Göttingen
- Medizinische Hochschule Hannover; Klinik für Dermatologie, Allergologie und Venerologie
- Universitatsklinik Heidelberg; Universitätshautklinik und Nationales Centrum für Tumorerkrankungen
- UKSH Kiel; Klinik für Dermatologie, Venerologie und Allergologie
- Klinikum d.Universität zu Köln Klinik u.Poliklinik f.Dermatologie
- Universitätsklinikum Leipzig; Klinik für Dermatologie, Venerologie und Allergologie
- UKSH Universitatsklinikum Schleswig-Holstein; Studienzentrum Dermatologie 10d
- Universitatsklinikum Mainz; Klinik und Poliklinik fur Dermatologie
- Klinikum der Ludwigs-Maximilians-Universität München; Dermatologie
- Fachklinik Hornheide; Dermatologie
- Harzklinikum Dorothea Christiane Erxleben GmbH, Standort Quedlinburg; Hautkrebszentrum Harz
- Universitätsklinikum Regensburg; Klinik und Poliklinik für Dermatologie
- Zentrum für Dermatoonkologie, Universitäts-Hautklinik Tübingen
- Universitätsklinikum Würzburg; Med. Klinik 1, Pneumologie
- Laiko General Hospital Athen
- Metropolitan Hospital; Dept. of Oncology
- Orszagos Onkologiai Intezet; Borgyogyaszati Osztaly
- University of Szeged Szent-Györgyi Albert Clinical Center; Department of Dermatology and Allergology
- Rambam Health Care Campus; Oncology
- Sharett Institute - Hadassah Hebrew University Medical Center
- Rabin MC; Davidof Center - Oncology Institute
- Ella Institute - Sheba Medical Center
- IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica B
- IRST Istituto Scientifico Romagnolo Per Lo Studio E Cura Dei Tumori, Sede Meldola; Oncologia Medica
- A.O. Universitaria S. Maria Della Misericordia Di Udine; Oncologia
- 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
- Istituto Tumori ?Giovanni Paolo II?, Oncologia
- A.O.U. Senese Policlinico Santa Maria Alle Scotte
- Seoul National University Hospital
- Severance Hospital, Yonsei University Health System
- Asan Medical Center
- Samsung Medical Center
- Erasmus Mc - Daniel Den Hoed Kliniek; Interne Oncologie
- Auckland city hospital; Auckland Regional Cancer Centre and Blood Service
- Wellington Hospital; Wellington Blood and Cancer Centre
- Mid Central DHB
- Tauranga Hospital, Clinical Trials Unit; BOP Clinical School
- Uniwersyteckie Centrum Kliniczne; Klinika Onkologii i Radioterapii
- Narodowy Inst.Onkol.im.Sk?odowskiej-Curie Pa?stw.Inst.Badawczy Kraków; Klinika Onkologii Klinicznej
- COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej
- Uniwersytecki Szpital Kliniczny w Poznaniu
- Narodowy Instytut Onkologii im. Marii Sk?odowskiej-Curie - Pa?stwowy Instytut Badawczy
- Dolno?l?skie Centrum Onkologii, Pulmonologii i Hematologii
- IPO de Lisboa; Servico de Oncologia Medica
- IPO do Porto; Servico de Oncologia Medica
- 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
- Clinica Universitaria de Navarra; Servicio de Oncologia
- Hospital Universitari Vall d'Hebron; Oncology
- Hospital Clínic i Provincial; Servicio de Oncología
- Hospital Ramon y Cajal; Servicio de Oncologia
- Hospital Universitario La Paz; Servicio de Oncologia
- Hospital Universitario Virgen de la Macarena;
- Fundacion Instituto Valenciano de Oncologia (IVO)
- Hospital General Universitario de Valencia; Servicio de oncologia
- Hospital Universitario Miguel Servet; Servicio Oncologia
- Bristol Haematology and Oncology centre
- Beatson West of Scotland Cancer Centre
- Ipswich Hospital; Oncology Pharmacy
- St James Uni Hospital; Icrf Cancer Medicine Research Unit
- Guys and St Thomas NHS Foundation Trust, Guys Hospital
- Freeman Hospital; Northern Centre For Cancer Care
- Singleton Hospital; Pharmacy Department
- Royal Cornwall Hospital
Arms of the Study
Arm 1
Arm 2
Experimental
Experimental
Atezolizumab + Cobimetinib + Vemurafenib + Vemurafenib Placebo
Atezolizumab Placebo + Cobimetinib + Vemurafenib
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.
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.