A Study to Investigate the Efficacy and Safety of Cobimetinib Plus Atezolizumab in Participants With Solid Tumors

NCT ID: NCT03264066

Last Updated: 2021-05-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 87 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-23
• Study Completion Date: 2020-06-25

Brief Summary

This is a study to evaluate the efficacy, safety, and pharmacokinetics of cobimetinib plus atezolizumab in participants with advanced solid tumors including the following cohorts: squamous cell carcinoma of the head and neck (SCCHN), urothelial carcinoma (UC), and renal cell carcinoma (RCC).

Conditions

Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1 - SCCHN - Treatment Naive

In participants with recurrent or advanced / metastatic SSCHN who are anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

Group Type: EXPERIMENTAL

Cobimetinib

Intervention Type: DRUG

Participants will receive cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1-21 of each 28-day cycle.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be given at a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

Cohort 2 - UC - Treatment Naive

In participants with advanced / metastatic UC who are anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

Group Type: EXPERIMENTAL

Cobimetinib

Intervention Type: DRUG

Participants will receive cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1-21 of each 28-day cycle.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be given at a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

Cohort 3 - RCC - Treatment Naive

In participants with metastatic RCC who are anti-PD-1 and anti-PD-L1 treatment naive, cobimetinib will be administered at the approved dose and schedule of 60 milligrams (mg) once daily (QD) for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

Group Type: EXPERIMENTAL

Cobimetinib

Intervention Type: DRUG

Participants will receive cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1-21 of each 28-day cycle.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be given at a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

Cohort 4 - SCCHN - Previous Treatment Exposure

In participants with SCCHN whose disease has progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

Group Type: EXPERIMENTAL

Cobimetinib

Intervention Type: DRUG

Participants will receive cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1-21 of each 28-day cycle.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be given at a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

Cohort 5 - UC - Previous Treatment Exposure

In participants with UC whose disease has progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

Group Type: EXPERIMENTAL

Cobimetinib

Intervention Type: DRUG

Participants will receive cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1-21 of each 28-day cycle.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be given at a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

Cohort 6 - RCC - Previous Treatment Exposure

In participants with RCC whose disease has progressed while receiving anti-PD-1 or anti-PD-L1 therapy, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle; and atezolizumab 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

Group Type: EXPERIMENTAL

Cobimetinib

Intervention Type: DRUG

Participants will receive cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1-21 of each 28-day cycle.

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be given at a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

Cohort 7 - Biopsy Cohort

In participants with solid non-melanoma, non- hematologic tumors who previously developed primary or secondary resistance to an anti-PD-1 or anti-PD-L1 agent, cobimetinib will be administered at the approved dose and schedule of 60 mg QD for 21 days and 7 days off of each 28-day cycle. The first dose of atezolizumab of 840 mg by IV infusions on Day 15 of Cycle 1. Thereafter, they will receive atezolizumab 840 mg IV infusion Q2W on Days 1 and 15 of Cycle 2 and all subsequent cycles.

Group Type: EXPERIMENTAL

Cobimetinib

Intervention Type: DRUG

Participants will receive cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1-21 of each 28-day cycle.

Atezolizumab Cohort 7

Intervention Type: DRUG

Only for participants in cohort 7, the first dose of atezolizumab of 840 mg will be given by IV infusion on Day 15 of Cycle 1; thereafter, they will receive atezolizumab 840 mg IV infusion Q2W on Days 1 and 15 of Cycle 2 and all subsequent cycles.

Interventions

Cobimetinib

Participants will receive cobimetinib 60 mg (3 tablets of 20 mg each) orally once a day on Days 1-21 of each 28-day cycle.

Intervention Type: DRUG

Atezolizumab

Atezolizumab will be given at a fixed dose of 840 mg by intravenous (IV) infusion on Days 1 and 15 of each 28-day cycle.

Intervention Type: DRUG

Atezolizumab Cohort 7

Only for participants in cohort 7, the first dose of atezolizumab of 840 mg will be given by IV infusion on Day 15 of Cycle 1; thereafter, they will receive atezolizumab 840 mg IV infusion Q2W on Days 1 and 15 of Cycle 2 and all subsequent cycles.

Intervention Type: DRUG

Other Intervention Names

Cotellic; Tecentriq; Tecentriq

Eligibility Criteria

Inclusion Criteria

• Age ≥18 years
• Ability to comply with the study protocol, in the investigator's judgment
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
• Life expectancy ≥3 months, as determined by the investigator
• Adequate hematologic and end-organ function

• Patients must have measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) scan per RECIST v1.1.
• Availability to provide a representative tumor specimen biopsy
• Evidence of tumor progression on or after the last treatment regimen received and within 6 months prior to study enrollment
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use a non-hormonal contraceptive method with a failure rate of <1% per year during the treatment period and for at least 5 months after the last dose of atezolizumab and within 3 months after the last dose of cobimetinib
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm during the treatment period and for at least 3 months after the last dose of cobimetinib

Exclusion Criteria

• Inability to swallow medications
• Malabsorption condition that would alter the absorption of orally administered medications
• Poor peripheral venous access
• Prior treatment with cobimetinib or a MEK inhibitor
• Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
• Treatment with investigational therapy within 14 days prior to initiation of study treatment
• Any anti-cancer therapy, including chemotherapy or hormonal therapy, within 2 weeks prior to initiation of study treatment
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to biopharmaceutical agents produced in Chinese hamster ovary cells or any component of the atezolizumab formulation, or any component of the cobimetinib formulation
• History of serous retinopathy, retinal vein occlusion (RVO), or evidence of ongoing serous retinopathy or RVO at baseline
• Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment, or anticipation of need for a major surgical procedure during the study
• Uncontrolled tumor-related pain
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage more than once every 28 days
• Uncontrolled hypercalcemia (ionized calcium >1.5 millimoles per liter [mmol/L], calcium >12 milligrams per deciliter [mg/dL], or corrected calcium greater than the upper limit of normal [ULN]) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy
• Active or untreated central nervous system (CNS) metastases
• Pregnancy or breastfeeding, or intending to become pregnant during the study

Cardiovascular

Patients who meet the following cardiovascular exclusion criterion will be excluded from study entry:

• Left ventricular ejection fraction (LVEF) below the institutional lower limit of normal or <50%, whichever is lower

• Positive human immunodeficiency virus (HIV) test at screening
• Active hepatitis B virus (HBV) infection (chronic or acute)
• Active hepatitis C virus (HCV) infection
• Active tuberculosis
• Severe infection within 4 weeks prior to initiation of study treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Georgetown University Medical Center

Washington D.C., District of Columbia, United States

Kansas City - Menorah Medical Center

Kansas City, Kansas, United States

Memorial Sloan-Kettering Cancer Center

Commack, New York, United States

Memorial Sloan Kettering - Basking Ridge

New York, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Sarah Cannon Research Institute

Nashville, Tennessee, United States

AZ Groeninge

Kortrijk, , Belgium

Universitatsklinik Heidelberg; Universitätshautklinik und Nationales Centrum für Tumorerkrankungen

Heidelberg, , Germany

Universitätsklinikum Tübingen; Klinik für Urologie

Tübingen, , Germany

Orszagos Onkologiai Intezet

Budapest, , Hungary

Debreceni Egyetem Klinikai Kozpont

Debrecen, , Hungary

Jósa András Oktatókórház

Nyíregyháza, , Hungary

Samsung Medical Center

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Yonsei Cancer Center

Seoul, , South Korea

Barts & London School of Med; Medical Oncology

London, , United Kingdom

Royal Marsden Hospital - Fulham

London, , United Kingdom

The Royal Marsden

London, , United Kingdom

Countries

United States; Belgium; Germany; Hungary; South Korea; United Kingdom

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

2017-000794-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

WO39760

Identifier Type: -

Identifier Source: org_study_id