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

NCT ID: NCT01988896

Last Updated: 2019-12-17

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

153 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-12-27

Study Completion Date

2019-11-04

Brief Summary

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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.

Detailed Description

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Conditions

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Solid Tumors

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dose-Escalation: Cobimetinib, Atezolizumab

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.

Group Type EXPERIMENTAL

Atezolizumab

Intervention Type DRUG

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

Cobimetinib

Intervention Type DRUG

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

Dose-Expansion: Cobimetinib, Atezolizumab

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.

Group Type EXPERIMENTAL

Atezolizumab

Intervention Type DRUG

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

Cobimetinib

Intervention Type DRUG

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

Interventions

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Atezolizumab

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

Intervention Type DRUG

Cobimetinib

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

Intervention Type DRUG

Other Intervention Names

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MPDL3280 GDC-0973

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
* Received therapeutic oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1
* Significant cardiovascular disease
* Major surgical procedure other than for diagnosis within 28 days prior to Cycle 1 Day 1 or anticipation of need for a major surgical procedure during the course of the study
* Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1


* History of prior significant toxicity from another mitogen-activated protein kinase (MEK) pathway inhibitor requiring discontinuation of treatment
* Allergy or hypersensitivity to components of the cobimetinib formulations
* History of congenital long QT syndrome or corrected QT interval (QTc) greater than (\>) 450 milliseconds at screening
* Left ventricular ejection fraction (LVEF) below institutional lower limit of normal (LLN) or below 50%, whichever is lower, as determined by echocardiogram or Multi Gated Acquisition Scan (MUGA) scan
* History of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment, central serous chorioretinopathy (CSCR), retinal vein occlusion (RVO), or neovascular macular degeneration
* History of malabsorption syndrome or other condition that would interfere with enteral absorption


* Prior treatment with clusters of differentiation (CD) 137 agonists or immune checkpoint blockade therapies, systemic immunostimulatory agents, or systemic immunosuppressive medications
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Hoffmann-La Roche

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

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Stanford University Medical Center

Palo Alto, California, United States

Site Status

Rocky Mountain Cancer Center - Denver

Denver, Colorado, United States

Site Status

Yale University School Of Medicine

New Haven, Connecticut, United States

Site Status

Massachusets General Hospital Clinical Trial Network and Institute

Boston, Massachusetts, United States

Site Status

Beth Israel Deaconess Med Ctr; Neurology/MS Center

Boston, Massachusetts, United States

Site Status

Sloan Kettering Cancer Center; Pediatric Hematology/Oncology

New York, New York, United States

Site Status

UNC Lineberger Comprehensive Cancer Center

Chapel Hill, North Carolina, United States

Site Status

Compass Oncology

Portland, Oregon, United States

Site Status

SCRI-Tennessee Oncology

Nashville, Tennessee, United States

Site Status

Texas Oncology, P.A.

Arlington, Texas, United States

Site Status

University of Washington Seattle Cancer Care Alliance

Seattle, Washington, United States

Site Status

Peter MacCallum Cancer Centre-East Melbourne

Melbourne, Victoria, Australia

Site Status

Royal Melbourne Hospital

Parkville, Victoria, Australia

Site Status

Princess Margaret Hospital; Department of Med Oncology

Toronto, Ontario, Canada

Site Status

CHUM Hôpital Notre-Dame

Montreal, Quebec, Canada

Site Status

Jewish General Hospital

Montreal, Quebec, Canada

Site Status

Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden

Dresden, , Germany

Site Status

Universitaetsklinikum Freiburg

Freiburg im Breisgau, , Germany

Site Status

National University Hospital; Cancer Center

Singapore, , Singapore

Site Status

Seoul National University Hospital

Seoul, , South Korea

Site Status

Asan Medical Center - Oncology

Seoul, , South Korea

Site Status

Countries

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Czechia France Spain Sweden United Kingdom United States Australia Canada Germany Singapore South Korea

References

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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.

Reference Type DERIVED
PMID: 30918950 (View on PubMed)

Other Identifiers

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2013-003329-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GP28363

Identifier Type: -

Identifier Source: org_study_id