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

NCT03264066 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: WO397602017-000794-37
• Study Type: interventional
• Target: 87
• Locations: 6 countries
• Sites: 19

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

Outcome Measures

Primary Outcomes (1)

• Objective Response Rate (ORR)

  Objective response rate was defined as the percentage of participants with a complete response (CR) or a partial response (PR) on two consecutive tumor assessments ≥4 weeks apart, as determined by the investigators using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). CR was defined as disappearance of all lesions. PR was defined as ≥30% decrease in the sum of diameters of target lesions, in the absence of CR, new lesions, and unequivocal progression in non-target lesions.

  Up to approximately 31 months

Secondary Outcomes (10)

• Overall Survival (OS)

  Up to approximately 31 months

• Progression-Free Survival (PFS)

  Up to approximately 31 months

• Duration of Response (DOR)

  Up to approximately 22 months

• Disease Control Rate (DCR)

  At 16 weeks

• Number of Participants With Adverse Events

  Up to approximately 31 months

Study Arms (7)

Cohort 1 - SCCHN - Treatment Naive

EXPERIMENTAL

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.

Drug: Cobimetinib; Drug: Atezolizumab

Cohort 2 - UC - Treatment Naive

EXPERIMENTAL

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.

Drug: Cobimetinib; Drug: Atezolizumab

Cohort 3 - RCC - Treatment Naive

EXPERIMENTAL

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.

Drug: Cobimetinib; Drug: Atezolizumab

Cohort 4 - SCCHN - Previous Treatment Exposure

EXPERIMENTAL

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.

Drug: Cobimetinib; Drug: Atezolizumab

Cohort 5 - UC - Previous Treatment Exposure

EXPERIMENTAL

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.

Drug: Cobimetinib; Drug: Atezolizumab

Cohort 6 - RCC - Previous Treatment Exposure

EXPERIMENTAL

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.

Drug: Cobimetinib; Drug: Atezolizumab

Cohort 7 - Biopsy Cohort

EXPERIMENTAL

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.

Drug: Cobimetinib; Drug: Atezolizumab Cohort 7

Interventions

Cobimetinib 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.

Also known as: Cotellic

Cohort 1 - SCCHN - Treatment Naive; Cohort 2 - UC - Treatment Naive; Cohort 3 - RCC - Treatment Naive; Cohort 4 - SCCHN - Previous Treatment Exposure; Cohort 5 - UC - Previous Treatment Exposure; Cohort 6 - RCC - Previous Treatment Exposure; Cohort 7 - Biopsy Cohort

Atezolizumab 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.

Also known as: Tecentriq

Cohort 1 - SCCHN - Treatment Naive; Cohort 2 - UC - Treatment Naive; Cohort 3 - RCC - Treatment Naive; Cohort 4 - SCCHN - Previous Treatment Exposure; Cohort 5 - UC - Previous Treatment Exposure; Cohort 6 - RCC - Previous Treatment Exposure

Atezolizumab Cohort 7 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.

Also known as: Tecentriq

Cohort 7 - Biopsy Cohort

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (19)

Georgetown University Medical Center

Washington D.C., District of Columbia, 20007, United States

Location

Kansas City - Menorah Medical Center

Kansas City, Kansas, 66209, United States

Location

Memorial Sloan-Kettering Cancer Center

Commack, New York, 11725, United States

Location

Memorial Sloan Kettering - Basking Ridge

New York, New York, 10065, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

AZ Groeninge

Kortrijk, 8500, Belgium

Location

Universitatsklinik Heidelberg; Universitätshautklinik und Nationales Centrum für Tumorerkrankungen

Heidelberg, 69120, Germany

Location

Universitätsklinikum Tübingen; Klinik für Urologie

Tübingen, 72076, Germany

Location

Orszagos Onkologiai Intezet

Budapest, 1122, Hungary

Location

Debreceni Egyetem Klinikai Kozpont

Debrecen, 4032, Hungary

Location

Jósa András Oktatókórház

Nyíregyháza, 4400, Hungary

Location

Samsung Medical Center

Seoul, (0)6351, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Yonsei Cancer Center

Seoul, 120-752, South Korea

Location

Barts & London School of Med; Medical Oncology

London, EC1A 7BE, United Kingdom

Location

Royal Marsden Hospital - Fulham

London, SW3 6JJ, United Kingdom

Location

The Royal Marsden

London, SW7 3RP, United Kingdom

Location

MeSH Terms

Interventions

cobimetinib; atezolizumab

Results Point of Contact

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

genentech@druginfo.com

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 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2017
• First Posted: August 28, 2017
• Study Start: November 23, 2017
• Primary Completion: June 25, 2020
• Study Completion: June 25, 2020
• Last Updated: May 11, 2021
• Results First Posted: March 1, 2021

Record last verified: 2021-04

Locations

GB (3); US (6); BE (1); HU (3); DE (2); KR (4)