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

NCT03273153 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: CO397222016-004387-18
• Study Type: interventional
• Target: 446
• Locations: 15 countries
• Sites: 121

Brief Summary

This is a Phase III, multicenter, open-label, randomized study designed to evaluate the efficacy, safety, and pharmacokinetics of cobimetinib plus atezolizumab compared with pembrolizumab in treatment-naive participants with advanced BRAFV600 wild-type melanoma.

Conditions

Advanced BRAFV600 Wild-type Melanoma

Outcome Measures

Primary Outcomes (1)

• 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 (15)

• PFS as Determined by the Investigator

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

• Objective Response as Determined by the Investigator

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

• Objective Response as Determined by IRC

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

• Disease Control Rate (DCR)

  Week 16

• Overall Survival (OS)

  From randomization up to approximately 3 years

Study Arms (2)

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

Interventions

Cobimetinib DRUG

Cobimetinib 60 mg tablets orally once daily on a 21 days on, 7 days off schedule.

Cobimetinib and Atezolizumab

Atezolizumab DRUG

Atezolizumab 840 mg as IV infusion once in every 2 weeks.

Cobimetinib and Atezolizumab

Pembrolizumab DRUG

Pembrolizumab 200 mg as IV infusion once in every 3 weeks.

Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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
• 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
• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (121)

University of Arizona Cancer Center

Tucson, Arizona, 85719, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

USC Norris Cancer Center

Los Angeles, California, 90033, United States

Location

USC Norris Cancer Center; USC Oncology Hematology Newport Beach

Newport Beach, California, 92663, United States

Location

University of California at Irvine Medical Center; Department of Oncology

Orange, California, 92868, United States

Location

Stanford Comprehensive Cancer Center

Stanford, California, 94305, United States

Location

UF Health Cancer Center at Orlando Health

Orlando, Florida, 32824, United States

Location

Florida Cancer Specialist, North Region

St. Petersburg, Florida, 33705, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Florida Cancer Specialists

West Palm Beach, Florida, 33401, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

Massachusetts General Hospital;Hematology/ Oncology

Boston, Massachusetts, 02114, United States

Location

University of Michigan; Michigan Institute for Clinical and Health Research (MICHR)

Ann Arbor, Michigan, 48109, United States

Location

Dartmouth-Hitchcock Medical Center; Hematology/Oncology

Lebanon, New Hampshire, 03756, United States

Location

Morristown Medical Center

Morristown, New Jersey, 07962, United States

Location

Forsythe Memorial Hospital Inc., dba Novant Health Oncology Specialists

Winston-Salem, North Carolina, 27103, United States

Location

TriHealth Hatton Institute; Surgical Education

Cincinnati, Ohio, 45220, United States

Location

St. Luke's University Health network

Bethlehem, Pennsylvania, 18015, United States

Location

Thomas Jefferson University Hospital;Medical Oncology

Philadelphia, Pennsylvania, 19107, United States

Location

SCRI Tennessee Oncology Chattanooga

Chattanooga, Tennessee, 37404, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

M.D Anderson Cancer Center; Uni of Texas At Houston

Houston, Texas, 77030, United States

Location

West Virginia University Hospitals Inc

Morgantown, West Virginia, 26056, United States

Location

Cairns Base Hospital

Cairns, Queensland, 4870, Australia

Location

Townsville General Hospital

Douglas, Queensland, 4184, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Royal Hobart Hospital

Hobart, Tasmania, 7000, Australia

Location

Fiona Stanley Hospital

Murdoch, Western Australia, 6150, Australia

Location

Cliniques Universitaires St-Luc

Brussels, 1200, Belgium

Location

AZ Groeninge

Kortrijk, 8500, Belgium

Location

UZ Leuven Gasthuisberg

Leuven, 3000, Belgium

Location

Instituto Nacional de Cancer - INCa; Oncologia

Rio de Janeiro, Rio de Janeiro, 20560-120, Brazil

Location

Hospital das Clinicas - UFRGS

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Hopital Avicenne; Dermatologie

Bobigny, 93009, France

Location

Hopital Saint Andre CHU De Bordeaux; Dermatologie

Bordeaux, 33075, France

Location

Chu Site Du Bocage;Dermatologie

Dijon, 21079, France

Location

CHU de Grenoble - Hôpital Nord

Grenoble, 38043, France

Location

Centre Hospitalier Le Mans; Dermatologie

Le Mans, 72037, France

Location

Hopital Claude Huriez; Sce Dermatologie

Lille, 59037, France

Location

Hopital Timone Adultes; Dermatologie

Marseille, 13385, France

Location

CHU de Nantes; Cancéro-dermatologie

Nantes, 44093, France

Location

Hopital l Archet 2; Ginestriere, Service de; Dermatologie

Nice, 06200, France

Location

Groupe Hospitalier Bichat Claude Bernard

Paris, 75018, France

Location

Hopital Saint Louis; Dermatologie 1

Paris, 75475, France

Location

Hopital Robert Debre; DERMATOLOGIE

Reims, 51092, France

Location

Centre Eugene Marquis; Service d'oncologie

Rennes, 35042, France

Location

Hopital Charles Nicolle; Dermatologie Serv.

Rouen, 76031, France

Location

Institut Universitaire du Cancer - Oncopole Toulouse (IUCT-O)

Toulouse, 31059, France

Location

Institut Gustave Roussy; Dermatologie

Villejuif, 94805, France

Location

Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik für Dermatologie

Dresden, 01307, Germany

Location

HELIOS Klinikum Erfurt; Klinik für Dermatologie & Allergologie

Erfurt, 99089, Germany

Location

Universitatsklinikum Essen; Klinik für Dermatologie

Essen, 45147, Germany

Location

Klinik Johann Wolfgang von Goethe Uni; Klinik für Dermatologie, Venerologie und Allergologie

Frankfurt, 60590, Germany

Location

SRH Wald-Klinikum Gera; Klinik für Hautkrankheiten und Allergologie

Gera, 07548, Germany

Location

Medizinische Hochschule Hannover; Klinik für Dermatologie, Allergologie und Venerologie

Hanover, 30625, Germany

Location

UKSH Kiel; Klinik für Dermatologie, Venerologie und Allergologie

Kiel, 24105, Germany

Location

Universitatsklinikum Mainz; Klinik und Poliklinik fur Dermatologie

Mainz, 55131, Germany

Location

Klinikum Mannheim Klinik fuer Dermatologie, Venerologie und Allergologie

Mannheim, 68167, Germany

Location

Johannes Wesling Klinikum Minden; Hämatologie, Onkologie, Hämostaseologie und Palliativmedizin

Minden, 32429, Germany

Location

Klinikum der Ludwigs-Maximilians-Universität München; Dermatologie

München, 80337, Germany

Location

Fachklinik Hornheide; Dermatologie

Münster, 48157, Germany

Location

Zentrum für Dermatoonkologie, Universitäts-Hautklinik Tübingen

Tübingen, 72076, Germany

Location

Anticancer Hospital Ag. Savas ; 2Nd Dept. of Oncology - Internal Medicine

Athens, 115 22, Greece

Location

Laiko General Hospital Athen

Athens, 115 27, Greece

Location

Metropolitan Hospital; Dept. of Oncology

Pireaus, 185 47, Greece

Location

Bioclinic Thessaloniki

Thessaloniki, 546 22, Greece

Location

Orszagos Onkologiai Intezet; Borgyogyaszati Osztaly

Budapest, 1122, Hungary

Location

Pecsi Tudomanyegyetem AOK; Borgyogyaszati Klinika

Pécs, 7632, Hungary

Location

University of Szeged Szent-Györgyi Albert Clinical Center; Department of Dermatology and Allergology

Szeged, 6720, Hungary

Location

A.O.U. Cons. Policlinico Bari - Consorzlale Policlinico; Scienze Biomediche e Oncologia Umana

Bari, Apulia, 70124, Italy

Location

Azienda Osp Uni Seconda Università Degli Studi Di Napoli; Unità Operativa Oncologia Medica

Napoli, Campania, 80131, Italy

Location

IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica B

Napoli, Campania, 80131, Italy

Location

A.O. Universitaria Policlinico Di Modena; Ematologia

Modena, Emilia-Romagna, 41124, Italy

Location

IFO - Istituto Regina Elena; Oncologia Medica

Rome, Lazio, 00144, Italy

Location

IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A

Genoa, Liguria, 16132, Italy

Location

Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2

Milan, Lombardy, 20133, Italy

Location

Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica

Milan, Lombardy, 20141, Italy

Location

Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico

Candiolo, Piedmont, 10060, Italy

Location

Azienda Ospedaliero - Universitaria Pisana U.O. Oncologia Medica 2 Universitaria - Polo Oncologico

Pisa, Tuscany, 56126, Italy

Location

IOV - Istituto Oncologico Veneto IRCCS

Padua, Veneto, 35128, Italy

Location

Antoni Van Leeuwenhoek Ziekenhuis; Inwendige Geneeskunde

Amsterdam, 1066 CX, Netherlands

Location

Amphia Ziekenhuis, locatie Langendijk;Oncology

Breda, 4818 CK, Netherlands

Location

Erasmus Mc - Daniel Den Hoed Kliniek; Interne Oncologie

Rotterdam, 3015AA, Netherlands

Location

Zuyderland ziekenhuis locatie Geleen

Sittard-Geleen, 6162 BG, Netherlands

Location

Copernicus Podmiot Medyczny Sp. z o.o. Wojewodzkie Centrum Onkologii

Gdansk, 80-219, Poland

Location

COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej

Lublin, 20-090, Poland

Location

Szpital Kliniczny im. Heliodora Święcickiego UM w Poznaniu.

Poznan, 60-780, Poland

Location

Zachodniopomorskie Centrum Onkologii, Osrodek Innowacyjnosci, Rozwoju i Badan Klinicznych

Szczecin, 71-730, Poland

Location

Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy

Warsaw, 02-781, Poland

Location

Dolnośląskie Centrum Onkologii, Pulmonologii i Hematologii

Wroclaw, 53-413, Poland

Location

Moscow City Oncology Hospital #62

Moscovskaya Oblast, Moscow Oblast, 143423, Russia

Location

FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"

Moscow, 115478, Russia

Location

St. Petersburg Oncology Hospital

Saint Petersburg, 198255, Russia

Location

FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"

Saint Petersburg, Russia

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 06351, South Korea

Location

Hospital Universitario Son Espases; Servicio de Oncologia

Palma de Mallorca, Balearic Islands, 07014, Spain

Location

Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia

Badalona, Barcelona, 08916, Spain

Location

Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia

Santiago de Compostela, LA Coruña, 15706, Spain

Location

Hospital Universitario Materno Infantil de Gran Canaria; Servicio de Oncologia

Las Palmas de Gran Canaria, LAS Palmas, 35016, Spain

Location

Clinica Universitaria de Navarra; Servicio de oncología

Pamplona, Navarre, 31008, Spain

Location

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, 08035, Spain

Location

Hospital Clínic i Provincial; Servicio de Oncología

Barcelona, 08036, Spain

Location

Hospital General Universitario Gregorio Marañon; Servicio de Oncologia

Madrid, 28007, Spain

Location

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre; Servicio de Oncologia

Madrid, 28041, Spain

Location

Hospital Universitario La Paz; Servicio de Oncologia

Madrid, 28046, Spain

Location

Hospital Universitario Virgen Macarena; Servicio de Oncologia

Seville, 41009, Spain

Location

Instituto Valenciano Oncologia; Oncologia Medica

Valencia, 46009, Spain

Location

Hospital General Universitario de Valencia; Servicio de oncologia

Valencia, 46014, Spain

Location

Hospital Universitario Miguel Servet; Servicio Oncologia

Zaragoza, 50009, Spain

Location

BRISTOL ONCOLOGY CENTRE; CLINICAL TRIALS UNIT; R & D department

Bristol, BS2 8HW, United Kingdom

Location

Western General Hospital; Edinburgh Cancer Center

Edinburgh, EH4 2XU, United Kingdom

Location

Leicester Royal Infirmary; Dept. of Medical Oncology

Leicester, LE1 5WW, United Kingdom

Location

University College London Hospital

London, NW1 - 2PG, United Kingdom

Location

Guys & St Thomas Hospital; Department of Oncology

London, SE1 9RT, United Kingdom

Location

University Hospitals of North Midlands NHS Trust-Royal Stoke University Hospital

Stoke-on-Trent, ST4 6QG, United Kingdom

Location

Singleton Hospital; Pharmacy

Swansea, SA2 8QA, United Kingdom

Location

Royal Cornwall Hospital

Truro, TR1 3LQ, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 33476492 DERIVED

MeSH Terms

Interventions

cobimetinib; atezolizumab; pembrolizumab

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

1-800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 1, 2017
• First Posted: September 6, 2017
• Study Start: December 11, 2017
• Primary Completion: April 15, 2019
• Study Completion: February 19, 2021
• Last Updated: September 21, 2022
• Results First Posted: June 9, 2020

Record last verified: 2022-08

Locations

US (23); PL (6); RU (4); DE (13); GR (4); NL (4); HU (3); FR (16); BR (2); BE (3); ES (15); GB (8); KR (4); IT (11); AU (5)