Study of Atezolizumab in Combination With Cobimetinib in Participants With Locally Advanced or Metastatic Solid Tumors

NCT01988896 | Completed Phase 1 FDA Drug

• 2 other identifiers: GP283632013-003329-27
• Study Type: interventional
• Target: 153
• Locations: 6 countries
• Sites: 21

Brief Summary

This is a Phase Ib, open-label, multicenter study designed to assess the safety, tolerability, and pharmacokinetics of coadministration of intravenous (IV) dosing of atezolizumab (an engineered anti-programmed death-ligand 1 \[anti-PD-L1\] antibody) and oral dosing of cobimetinib in participants with metastatic or locally advanced cancer for which no standard therapy exists.

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (3)

• Phase I: Percentage of Participants With Dose-Limiting Toxicities (DLTs)

  Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase

• Phase I: Maximum Tolerated Dose of Cobimetinib

  Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase

• Phase I: Recommended Phase II Dose of Cobimetinib when Combined with Atezolizumab

  Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase

Secondary Outcomes (12)

• Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Azetolizumab

  Pre-infusion (Hour 0) on Day 1 of Cycles 1, 2, 3, 4, 8 (cycle length=42 days for Cycle 1; 28 days for subsequent cycles) and at treatment completion visit (up to approximately 3.5 years)

• Percentage of Participants With Adverse Events (AEs) or Serious AEs (SAEs)

  Baseline up to approximately 3.5 years

• Serum Maximum Concentration (Cmax) of Atezolizumab

  Pre-infusion (Hour 0) on Day 1 of Cycles 2, 3, 4, 8 (cycle length=28 days) and at treatment completion visit (up to approximately 3.5 years); 30 minutes post-infusion (duration=60 minutes) on Cycle 1 Day 1 (cycle length=42 days)

• Serum Minimum Concentration (Cmin) of Atezolizumab

  Pre-infusion (Hour 0) on Day 1 of Cycles 2, 3, 4, 8 (cycle length=28 days) and at treatment completion visit (up to approximately 3.5 years)

• Plasma Cmax of Cobimetinib

  Pre-dose (Hour 0) and Hours 2, 4, 6 post-dose on Day 29 of Cycle 1 (cycle length=42 days) and Day 15 of Cycle 2 (cycle length=28 days)

Study Arms (2)

Dose-Escalation: Cobimetinib, Atezolizumab

EXPERIMENTAL

Participants will receive single dose of 800 milligrams (mg) of atezolizumab IV infusion on Day 1, 15 and 29 of Cycle 1 (cycle length=42 days \[14-day run-in period + 28-day concomitant dosing period\]), thereafter with atezolizumab IV dosing every 2 weeks (q2w) in all subsequent treatment cycles (28 days each). Combination with cobimetinib will begin on Cycle 1 Day 15 and will be given at increasing dose levels during Stage 1. During Stage 1, cobimetinib will be administered once daily (QD) orally for 21 consecutive days out of 28 days (21/7 dosing schedule) at a starting dose of 20 mg with escalation of 20 mg until the maximum tolerated dose (MTD; not more than 60 mg) for the two-drug combination.

Drug: Atezolizumab; Drug: Cobimetinib

Dose-Expansion: Cobimetinib, Atezolizumab

EXPERIMENTAL

Participants will receive single dose of 800 mg of atezolizumab IV infusion q2w in all subsequent treatment cycles (28 days each). Participants will receive cobimetinib at the selected recommended RP2D on Days 1-14 of each 28-day cycle during Stage 2.

Drug: Atezolizumab; Drug: Cobimetinib

Interventions

Atezolizumab DRUG

Atezolizumab will be administered at a fixed dose as specified via IV infusion.

Also known as: MPDL3280

Dose-Escalation: Cobimetinib, Atezolizumab; Dose-Expansion: Cobimetinib, Atezolizumab

Cobimetinib DRUG

Cobimetinib will be administered orally at an escalating dose during Stage 1 and at RP2D during Stage 2.

Also known as: GDC-0973

Dose-Escalation: Cobimetinib, Atezolizumab; Dose-Expansion: Cobimetinib, Atezolizumab

Eligibility Criteria

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

You may qualify if:

• Solid tumor that is metastatic, locally advanced or recurrent
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Life expectancy greater than or equal to (\>/=) 12 weeks
• Measurable disease, as defined by RECIST v 1.1
• Adequate hematologic and end organ function
• Use of highly effective contraception
• Histological tumor tissue specimen
• Participants enrolling in the indication-specific expansion cohorts in Stage 2 must consent to tumor biopsies and must have one of the following types of cancer:
• Metatastic colorectal cancer
• Non-small cell lung cancer
• Melanoma

You may not qualify if:

• Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment
• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrollment
• Known active or untreated central nervous system (CNS) metastases
• Leptomeningeal disease
• Uncontrolled tumor-related pain or uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent (once monthly or more frequently) drainage procedures
• Uncontrolled hypercalcemia or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab
• Pregnant and lactating women
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cell or any component of the atezolizumab formulation
• History of autoimmune disease
• Participants with prior allogeneic stem cell or solid organ transplantation
• Positive test for human immunodeficiency virus (HIV)
• Participants with active hepatitis B, hepatitis C, or tuberculosis
• Severe infections within 4 weeks prior to Cycle 1 Day 1
• Signs or symptoms of infection within 2 weeks prior to Cycle 1 Day 1

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (21)

Stanford University Medical Center

Palo Alto, California, 94304, United States

Location

Rocky Mountain Cancer Center - Denver

Denver, Colorado, 80220, United States

Location

Yale University School Of Medicine

New Haven, Connecticut, 06510, United States

Location

Massachusets General Hospital Clinical Trial Network and Institute

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Med Ctr; Neurology/MS Center

Boston, Massachusetts, 02215, United States

Location

Sloan Kettering Cancer Center; Pediatric Hematology/Oncology

New York, New York, 10065, United States

Location

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, 27514, United States

Location

Compass Oncology

Portland, Oregon, 97225, United States

Location

SCRI-Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Texas Oncology, P.A.

Arlington, Texas, 76012, United States

Location

University of Washington Seattle Cancer Care Alliance

Seattle, Washington, 98195, United States

Location

Peter MacCallum Cancer Centre-East Melbourne

Melbourne, Victoria, 3000, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Princess Margaret Hospital; Department of Med Oncology

Toronto, Ontario, M5G 2M9, Canada

Location

CHUM Hôpital Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden

Dresden, 01307, Germany

Location

Universitaetsklinikum Freiburg

Freiburg im Breisgau, 79106, Germany

Location

National University Hospital; Cancer Center

Singapore, 119074, Singapore

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center - Oncology

Seoul, 05505, South Korea

Location

Related Publications (1)

• Hellmann MD, Kim TW, Lee CB, Goh BC, Miller WH Jr, Oh DY, Jamal R, Chee CE, Chow LQM, Gainor JF, Desai J, Solomon BJ, Das Thakur M, Pitcher B, Foster P, Hernandez G, Wongchenko MJ, Cha E, Bang YJ, Siu LL, Bendell J. Phase Ib study of atezolizumab combined with cobimetinib in patients with solid tumors. Ann Oncol. 2019 Jul 1;30(7):1134-1142. doi: 10.1093/annonc/mdz113.

  PMID: 30918950 DERIVED

MeSH Terms

Interventions

atezolizumab; cobimetinib

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

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: November 14, 2013
• First Posted: November 20, 2013
• Study Start: December 27, 2013
• Primary Completion: November 4, 2019
• Study Completion: November 4, 2019
• Last Updated: December 17, 2019

Record last verified: 2019-12

Locations

US (11); AU (2); KR (2); DE (2); CA (3); SG (1)