Clinical trial NCT03273153: A Study of Cobimetinib Plus Atezolizumab Versus Pembrolizumab in Participants With Previously Untreated Advanced BRAFv600 Wild-Type Melanoma
Official title: A Phase III, Open-Label, Multicenter, Two Arm, Randomized Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab Versus Pembrolizumab in Patients With Previously Untreated Advanced BRAF V600 Wild-Type Melanoma
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Advanced BRAFV600 Wild-type Melanoma
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2017-09-06
Enrollment: 446
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Progression Free Survival (PFS) as Determined by the Independent Review Committee (IRC)
timeFrame: Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
Secondary outcomes:
measure: PFS as Determined by the Investigator
timeFrame: Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
measure: Objective Response as Determined by the Investigator
timeFrame: Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
measure: Objective Response as Determined by IRC
timeFrame: Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
measure: Disease Control Rate (DCR)
timeFrame: Week 16
measure: Overall Survival (OS)
timeFrame: From randomization up to approximately 3 years
measure: Duration of Objective Response Determined by the IRC
timeFrame: Every 8 weeks (wks) from Day (D) 1 of Cycle (C) 1 through approximately 16 months
measure: Duration of Objective Response Determined by the Investigator
timeFrame: Up to 3 years
measure: Two-year Landmark Survival
timeFrame: At 2 years
measure: Change From Baseline in Health-related Quality of Life (HRQoL) Scores
timeFrame: 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.
measure: Number of Participants With Adverse Events (AEs)
timeFrame: Up to approximately 16 months
measure: Number of Participants With Abnormal Vital Signs
timeFrame: From baseline up to approximately 3 years
measure: Number of Participants With Laboratory Abnormalities
timeFrame: Up to approximately 16 months
measure: Plasma Concentration of Cobimetinib
timeFrame: Days 1 and 15 of Cycle 1
measure: Serum Concentration of Atezolizumab
timeFrame: Day 1 of Cycles 1, 2, and 3
measure: Percentage of Participants With Anti-drug Antibodies (ADAs)
timeFrame: Day 1 of Cycle 1, 2, 3 and 30 days after treatment discontinuation
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona Cancer Center
state: Arizona
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: USC Norris Cancer Center
state: California
city: Newport Beach
country: United States
facility: USC Norris Cancer Center; USC Oncology Hematology Newport Beach
state: California
city: Orange
country: United States
facility: University of California at Irvine Medical Center; Department of Oncology
state: California
city: Stanford
country: United States
facility: Stanford Comprehensive Cancer Center
state: California
city: Orlando
country: United States
facility: UF Health Cancer Center at Orlando Health
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialist, North Region
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: West Palm Beach
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Boston
country: United States
facility: Massachusetts General Hospital;Hematology/ Oncology
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan; Michigan Institute for Clinical and Health Research (MICHR)
state: Michigan
city: Lebanon
country: United States
facility: Dartmouth-Hitchcock Medical Center; Hematology/Oncology
state: New Hampshire
city: Morristown
country: United States
facility: Morristown Medical Center
state: New Jersey
city: Winston-Salem
country: United States
facility: Forsythe Memorial Hospital Inc., dba Novant Health Oncology Specialists
state: North Carolina
city: Cincinnati
country: United States
facility: TriHealth Hatton Institute; Surgical Education
state: Ohio
city: Bethlehem
country: United States
facility: St. Luke's University Health network
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital;Medical Oncology
state: Pennsylvania
city: Chattanooga
country: United States
facility: SCRI Tennessee Oncology Chattanooga
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: M.D Anderson Cancer Center; Uni of Texas At Houston
state: Texas
city: Morgantown
country: United States
facility: West Virginia University Hospitals Inc
state: West Virginia
city: Cairns
country: Australia
facility: Cairns Base Hospital
state: Queensland
city: Douglas
country: Australia
facility: Townsville General Hospital
state: Queensland
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Hobart
country: Australia
facility: Royal Hobart Hospital
state: Tasmania
city: Murdoch
country: Australia
facility: Fiona Stanley Hospital
state: Western Australia
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires St-Luc
city: Kortrijk
country: Belgium
facility: AZ Groeninge
city: Leuven
country: Belgium
facility: UZ Leuven Gasthuisberg
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Cancer - INCa; Oncologia
state: RJ
city: Porto Alegre
country: Brazil
facility: Hospital das Clinicas - UFRGS
state: RS
city: Bobigny
country: France
facility: Hopital Avicenne; Dermatologie
city: Bordeaux
country: France
facility: Hopital Saint Andre CHU De Bordeaux; Dermatologie
city: Dijon
country: France
facility: Chu Site Du Bocage;Dermatologie
city: Grenoble
country: France
facility: CHU de Grenoble - Hôpital Nord
city: Le Mans
country: France
facility: Centre Hospitalier Le Mans; Dermatologie
city: Lille
country: France
facility: Hopital Claude Huriez; Sce Dermatologie
city: Marseille
country: France
facility: Hopital Timone Adultes; Dermatologie
city: Nantes
country: France
facility: CHU de Nantes; Cancéro-dermatologie
city: Nice cedex 3
country: France
facility: Hopital l Archet 2; Ginestriere, Service de; Dermatologie
city: Paris
country: France
facility: Groupe Hospitalier Bichat Claude Bernard
city: Paris
country: France
facility: Hopital Saint Louis; Dermatologie 1
city: Reims
country: France
facility: Hopital Robert Debre; DERMATOLOGIE
city: Rennes
country: France
facility: Centre Eugene Marquis; Service d'oncologie
city: Rouen
country: France
facility: Hopital Charles Nicolle; Dermatologie Serv.
city: Toulouse
country: France
facility: Institut Universitaire du Cancer - Oncopole Toulouse (IUCT-O)
city: Villejuif
country: France
facility: Institut Gustave Roussy; Dermatologie
city: Dresden
country: Germany
facility: Universitätsklinikum "Carl Gustav Carus"; Klinik und Poliklinik für Dermatologie
city: Erfurt
country: Germany
facility: HELIOS Klinikum Erfurt; Klinik für Dermatologie & Allergologie
city: Essen
country: Germany
facility: Universitatsklinikum Essen; Klinik für Dermatologie
city: Frankfurt
country: Germany
facility: Klinik Johann Wolfgang von Goethe Uni; Klinik für Dermatologie, Venerologie und Allergologie
city: Gera
country: Germany
facility: SRH Wald-Klinikum Gera; Klinik für Hautkrankheiten und Allergologie
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover; Klinik für Dermatologie, Allergologie und Venerologie
city: Kiel
country: Germany
facility: UKSH Kiel; Klinik für Dermatologie, Venerologie und Allergologie
city: Mainz
country: Germany
facility: Universitatsklinikum Mainz; Klinik und Poliklinik fur Dermatologie
city: Mannheim
country: Germany
facility: Klinikum Mannheim Klinik fuer Dermatologie, Venerologie und Allergologie
city: Minden
country: Germany
facility: Johannes Wesling Klinikum Minden; Hämatologie, Onkologie, Hämostaseologie und Palliativmedizin
city: München
country: Germany
facility: Klinikum der Ludwigs-Maximilians-Universität München; Dermatologie
city: Münster
country: Germany
facility: Fachklinik Hornheide; Dermatologie
city: Tübingen
country: Germany
facility: Zentrum für Dermatoonkologie, Universitäts-Hautklinik Tübingen
city: Athens
country: Greece
facility: Anticancer Hospital Ag. Savas ; 2Nd Dept. of Oncology - Internal Medicine
city: Athens
country: Greece
facility: Laiko General Hospital Athen
city: Pireaus
country: Greece
facility: Metropolitan Hospital; Dept. of Oncology
city: Thessaloniki
country: Greece
facility: Bioclinic Thessaloniki
city: Budapest
country: Hungary
facility: Orszagos Onkologiai Intezet; Borgyogyaszati Osztaly
city: Pecs
country: Hungary
facility: Pecsi Tudomanyegyetem AOK; Borgyogyaszati Klinika
city: Szeged
country: Hungary
facility: University of Szeged Szent-Györgyi Albert Clinical Center; Department of Dermatology and Allergology
city: Napoli
country: Italy
facility: Azienda Osp Uni Seconda Università Degli Studi Di Napoli; Unità Operativa Oncologia Medica
state: Campania
city: Napoli
country: Italy
facility: IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica B
state: Campania
city: Modena
country: Italy
facility: A.O. Universitaria Policlinico Di Modena; Ematologia
state: Emilia-Romagna
city: Roma
country: Italy
facility: IFO - Istituto Regina Elena; Oncologia Medica
state: Lazio
city: Genova
country: Italy
facility: IRCCS Istituto Nazionale Per La Ricerca Sul Cancro (IST); Oncologia Medica A
state: Liguria
city: Milano
country: Italy
facility: Irccs Istituto Nazionale Dei Tumori (Int);S.C. Medicina Oncologica 2
state: Lombardia
city: Milano
country: Italy
facility: Irccs Istituto Europeo Di Oncologia (IEO); Oncologia Medica
state: Lombardia
city: Candiolo
country: Italy
facility: Fondazione Del Piemonte Per L'oncologia Ircc Di Candiolo; Dipartimento Oncologico
state: Piemonte
city: Bari
country: Italy
facility: A.O.U. Cons. Policlinico Bari - Consorzlale Policlinico; Scienze Biomediche e Oncologia Umana
state: Puglia
city: Pisa
country: Italy
facility: Azienda Ospedaliero - Universitaria Pisana U.O. Oncologia Medica 2 Universitaria - Polo Oncologico
state: Toscana
city: Padova
country: Italy
facility: IOV - Istituto Oncologico Veneto IRCCS
state: Veneto
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Amsterdam
country: Netherlands
facility: Antoni Van Leeuwenhoek Ziekenhuis; Inwendige Geneeskunde
city: Breda
country: Netherlands
facility: Amphia Ziekenhuis, locatie Langendijk;Oncology
city: Rotterdam
country: Netherlands
facility: Erasmus Mc - Daniel Den Hoed Kliniek; Interne Oncologie
city: Sittard-Geleen
country: Netherlands
facility: Zuyderland ziekenhuis locatie Geleen
city: Gdansk
country: Poland
facility: Copernicus Podmiot Medyczny Sp. z o.o. Wojewodzkie Centrum Onkologii
city: Lublin
country: Poland
facility: COZL Oddzial Onkologii Klinicznej z pododdzialem Chemioterapii Dziennej
city: Poznań
country: Poland
facility: Szpital Kliniczny im. Heliodora Święcickiego UM w Poznaniu.
city: Szczecin
country: Poland
facility: Zachodniopomorskie Centrum Onkologii, Osrodek Innowacyjnosci, Rozwoju i Badan Klinicznych
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie - Państwowy Instytut Badawczy
city: Wrocław
country: Poland
facility: Dolnośląskie Centrum Onkologii, Pulmonologii i Hematologii
city: Moscovskaya Oblast
country: Russian Federation
facility: Moscow City Oncology Hospital #62
state: Moskovskaja Oblast
city: Moscow
country: Russian Federation
facility: FSBSI "Russian Oncological Scientific Center n.a. N.N. Blokhin"
city: Saint-Petersburg
country: Russian Federation
facility: FBI "Scientific Research Institute of Oncology n. a. N. N. Petrov"
city: St Petersburg
country: Russian Federation
facility: St. Petersburg Oncology Hospital
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol; Servicio de Oncologia
state: Barcelona
city: Palma De Mallorca
country: Spain
facility: Hospital Universitario Son Espases; Servicio de Oncologia
state: Islas Baleares
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario de Santiago (CHUS) ; Servicio de Oncologia
state: LA Coruña
city: Las Palmas de Gran Canaria
country: Spain
facility: Hospital Universitario Materno Infantil de Gran Canaria; Servicio de Oncologia
state: LAS Palmas
city: Pamplona
country: Spain
facility: Clinica Universitaria de Navarra; Servicio de oncología
state: Navarra
city: Barcelona
country: Spain
facility: Hospital Univ Vall d'Hebron; Servicio de Oncologia
city: Barcelona
country: Spain
facility: Hospital Clínic i Provincial; Servicio de Oncología
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre; Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario La Paz; Servicio de Oncologia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena; Servicio de Oncologia
city: Valencia
country: Spain
facility: Instituto Valenciano Oncologia; Oncologia Medica
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia; Servicio de oncologia
city: Zaragoza
country: Spain
facility: Hospital Universitario Miguel Servet; Servicio Oncologia
city: Bristol
country: United Kingdom
facility: BRISTOL ONCOLOGY CENTRE; CLINICAL TRIALS UNIT; R & D department
city: Edinburgh
country: United Kingdom
facility: Western General Hospital; Edinburgh Cancer Center
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary; Dept. of Medical Oncology
city: London
country: United Kingdom
facility: University College London Hospital
city: London
country: United Kingdom
facility: Guys & St Thomas Hospital; Department of Oncology
city: Stoke-On-Trent
country: United Kingdom
facility: University Hospitals of North Midlands NHS Trust-Royal Stoke University Hospital
city: Swansea
country: United Kingdom
facility: Singleton Hospital; Pharmacy
city: Truro
country: United Kingdom
facility: Royal Cornwall Hospital
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_CHAIR
References:
citation: 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.