Cobimetinib (Targeted Therapy) Plus Atezolizumab (Immunotherapy) in Participants With Advanced Melanoma Whose Cancer Has Worsened During or After Treatment With Previous Immunotherapy and Atezolizumab Monotherapy in Participants With Previously Untreated Advanced Melanoma

NCT03178851 | Completed Phase 1 Results FDA Drug

• 2 other identifiers: CO397212016-004402-34
• Study Type: interventional
• Target: 155
• Locations: 7 countries
• Sites: 43

Brief Summary

This study will evaluate the preliminary efficacy, safety, and pharmacokinetics of cobimetinib and atezolizumab in participants with advanced BRAF V600-wild type (WT), metastatic, or unresectable locally advanced melanoma who have progressed on prior anti-PD-1 therapy. In addition, this study will evaluate the efficacy, safety, and pharmacokinetics of atezolizumab monotherapy in participants with BRAFV600-WT metastatic or unresectable locally advanced melanoma, who have not been previously treated.

Conditions

Malignant Melanoma

Outcome Measures

Primary Outcomes (2)

• Investigator-Assessed Objective Response Rate (ORR)

  ORR is defined as the percentage of participants with confirmed objective response (OR). Confirmed OR is defined as complete response (CR) or partial response (PR) on two consecutive occasions ≥ 4 weeks apart, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters.

  Up to approximately 2 years

• Investigator-Assessed Disease Control Rate (DCR)

  DCR is defined as the percentage of participants with CR, PR, or stable disease (SD) at 16 weeks. Per RECIST v1.1, CR is defined as disappearance of all target lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. SD is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression, taking as reference the smallest sum on study. Disease progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study including baseline, or the appearance of one or more new lesions.

  Week 16

Secondary Outcomes (11)

• Investigator-Assessed Duration of Response (DOR)

  Up to approximately 2 years

• Overall Survival (OS)

  Up to approximately 2 years

• Investigator-Assessed Progression-Free Survival (PFS)

  Up to approximately 2 years

• Serum Concentration of Atezolizumab

  Cycle 1, Day 15; Day 1 of Cycles 2, 3, 4, 8

• Plasma Concentration of Cobimetinib

  Cycle 1, Day 15

Study Arms (3)

Cohort A

EXPERIMENTAL

Participants with disease progression on or after treatment with an anti-PD-1 agent will receive cobimetinib and atezolizumab treatment during 28-day cycles.

Biological: Atezolizumab; Drug: Cobimetinib

Cohort B

EXPERIMENTAL

Participants with disease progression on or after treatment with an anti-PD-1 agent will receive cobimetinib prior to initiating atezolizumab treatment during Cycle 1. During subsequent 28-day cycles participants will initiate both atezolizumab and cobimetinib on Day 1 of each cycle. Participants in this cohort will undergo tumor biopsies before and during treatment.

Drug: Cobimetinib; Biological: Atezolizumab

Cohort C

EXPERIMENTAL

Participants with advanced melanoma, who have not received previous treatment, will receive atezolizumab monotherapy during 21-day cycles.

Biological: Atezolizumab

Interventions

Atezolizumab BIOLOGICAL

Atezolizumab, 840 mg intravenously every two weeks (Q2W) on Days 1 and 15 of each 28-day cycle, until loss of clinical benefit

Also known as: Tecentriq

Cohort A

Cobimetinib DRUG

Cobimetinib, 60 mg orally once daily (QD) on Days 1-21 of each 28-day cycle, until loss of clinical benefit

Also known as: Cotellic

Cohort A; Cohort B

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed Stage IV (metastatic) or unresectable Stage IIIc BRAF V600 WT (locally advanced) melanoma
• Documentation of BRAF V600 mutation-negative status in melanoma tumor tissue (archival \[\< 5 years old\] or newly obtained) through use of a clinical mutation test approved by the local health authority
• Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
• Disease progression on or after treatment with a programmed death (PD)-1 inhibitor either as monotherapy or in combination with other agent(s)
• Progressed on or after anti-PD-1 therapy within 12 weeks before study start
• Received a minimum of two cycles of anti-PD-1 therapy
• Meet the following criteria for resistance to an anti-PD-1 agent: primary resistance defined as disease progression, according to RECIST v1.1, as best response; secondary resistance defined as disease progression after initial confirmed response according to RECIST v1.1
• Consent to undergo tumor biopsies of accessible lesions, before and during treatment and at radiographic progression, for biomarker analyses.
• Have at least two accessible lesions that are amenable to excisional or core-needle (minimum three cores and minimum diameter 18 gauge; however, 16 gauge is desirable) biopsy without unacceptable risk of a major procedural complication. Exceptions may be made if patient has only one lesion that allows multiple biopsies.
• Histologically confirmed Stage IV (metastatic) or unresectable Stage IIIc BRAFV600-WT (locally advanced) melanoma
• Naive to prior systemic anti-cancer therapy for melanoma
• Documentation of BRAFV600 mutation-negative status in melanoma tumor tissue (archival \[\< 5 years old\] or newly obtained) 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.
• Measurable disease according to RECIST v1.1.
• Ability to comply with the study protocol, in the investigator's judgment

You may not qualify if:

• Prior treatment with a mitogen activated-protein kinase (MAPK) inhibitor
• Ocular melanoma
• Major surgical procedure other than for diagnosis within 4 weeks before initiation of study treatment, or anticipation of need for a major surgical procedure during the course of the study
• Traumatic injury within 2 weeks before initiation of study treatment
• Palliative radiotherapy within 14 days before initiation of study treatment
• Active malignancy (other than BRAF V600 mutation-negative melanoma) or malignancy within 3 years
• Treatment with any anti-cancer agent 14 days prior to Cycle, Day 1 other than aPD-1 based therapy
• Adverse events from prior anti-cancer therapy that have not resolved to Grade ≤ 1. Clinically stable patients with manageable immune-related adverse events resulting from prior cancer immunotherapy may be eligible for the study.
• For Cohort C only: any prior anti-cancer therapy for advanced melanoma
• History or evidence of ongoing serous retinopathy or retinal vein occlusion (RVO) at baseline
• History of clinically significant cardiac dysfunction
• Active or untreated central nervous system (CNS) metastases
• History of metastases to brain stem, midbrain, pons, or medulla, or within 10 millimeter (mm) of the optic apparatus (optic nerves and chiasm)
• History of leptomeningeal metastatic disease
• Human immunodeficiency virus (HIV) infection

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (43)

HonorHealth Research Institute - Bisgrove

Scottsdale, Arizona, 85258, United States

Location

University of Colorado Hospital - Anschutz Cancer Pavilion

Aurora, Colorado, 80045, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Baylor University Medical Center

Dallas, Texas, 75231, United States

Location

Blacktown Hospital

Blacktown, New South Wales, 2148, Australia

Location

Melanoma Institute Australia

North Sydney, New South Wales, 2060, Australia

Location

Mid North Coast Cancer Institute

Port Macquarie, New South Wales, 2444, Australia

Location

Greenslopes Private Hospital; Clinic Pharmacy

Greenslopes, Queensland, 4120, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

Peter Maccallum Cancer Centre

Melbourne, Victoria, 3000, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

University Clinical Centre of the Republic of Srpska

Banja Luka, 78000, Bosnia and Herzegovina

Location

University Clinic Ctr Sarajevo

Sarajevo, 71 000, Bosnia and Herzegovina

Location

Instituto de Ensino e Pesquisa Clinica do Ceara

Fortaleza, Ceará, 60130-241, Brazil

Location

Cenantron - Centro Avancado de Tratamento Oncologico

Belo Horizonte, Minas Gerais, 30130-090, Brazil

Location

Instituto Nacional de Cancer - INCa; Oncologia

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

Location

Hospital Sao Vicente de Paulo

Passo Fundo, Rio Grande do Sul, 99010-090, Brazil

Location

Hospital das Clinicas - UFRGS

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

Location

Hospital Sao Lucas - PUCRS

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Hospital Amaral Carvalho

Jaú, São Paulo, 17210-120, Brazil

Location

Cape Town Oncology Trials

Cape Town, 7570, South Africa

Location

GVI Constantiaberg

Cape Town, 7800, South Africa

Location

Johese Clinical Research

Centurion, 1692, South Africa

Location

Cancercare

George, 6529, South Africa

Location

Wits Clinical Research; Charlotte Maxeke Johannesburg Academic Hospital

Johannesburg, 2193, South Africa

Location

Cancercare

Port Elizabeth, 6045, South Africa

Location

Steve Biko Academic Hospital; Oncology

Pretoria, 0002, South Africa

Location

Hospital Clinico Universitario de Santiago

Santiago de Compostela, LA Coruña, 15706, Spain

Location

Clínica Universidad de Navarra

Pamplona, Navarre, 31620, Spain

Location

Hospital Universitario Virgen Macarena

Seville, Sevilla, 41071, Spain

Location

Hospital Universitari Quiron Dexeus

Barcelona, 08028, Spain

Location

Hospital Clinic I Provincial

Barcelona, 08036, Spain

Location

MD Anderson Cancer Center

Madrid, 28033, Spain

Location

Hospital Universitario Ramón y Cajal; Pharmacy

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

Central Municipal Hospital - Uzhgorod State University

Uzhhorod, Chernihiv Governorate, 88017, Ukraine

Location

Public Institution: City Multispecialty Clinical Hospital #4 under Dnipropetrovsk Regional Council

Dnipropetrovsk, 49102, Ukraine

Location

National Cancer Institute MOH of Ukraine

Kiev, 36022, Ukraine

Location

Lviv State Oncology Regional Treatment and Diagnostic Centre

Lviv, 79031, Ukraine

Location

Sumy Regional Clinical Onc Ctr

Sumy, 40005, Ukraine

Location

Related Publications (3)

• Sandhu S, Atkinson V, Cao MG, Medina T, Rivas AS, Menzies AM, Caro I, Roberts L, Song Y, Yan Y, Guo Y, Xue C, Long GV. Phase 1b study of cobimetinib plus atezolizumab in patients with advanced BRAFV600 wild-type melanoma progressing on prior anti-programmed death-1 therapy. Eur J Cancer. 2023 Jan;178:180-190. doi: 10.1016/j.ejca.2022.10.019. Epub 2022 Nov 2.

  PMID: 36455412 DERIVED

• Barteselli G, Goodman GR, Patel Y, Caro I, Xue C, McCallum S. Characterization of Serous Retinopathy Associated with Cobimetinib: Integrated Safety Analysis of Four Studies. Drug Saf. 2022 Dec;45(12):1491-1499. doi: 10.1007/s40264-022-01248-2. Epub 2022 Oct 30.

  PMID: 36310331 DERIVED

• 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

Conditions

Melanoma

Interventions

atezolizumab; cobimetinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

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 DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 1, 2017
• First Posted: June 7, 2017
• Study Start: June 20, 2017
• Primary Completion: May 29, 2019
• Study Completion: September 21, 2020
• Last Updated: November 19, 2021
• Results First Posted: June 12, 2020

Record last verified: 2021-11

Locations

BR (7); US (6); ES (9); BO (2); ZA (7); AU (7); UA (5)