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

December 16, 2019 updated by: Hoffmann-La Roche

A Phase Ib Study of the Safety and Pharmacology of Atezolizumab Administered With Cobimetinib in Patients With Locally Advanced or Metastatic Solid Tumors

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
153

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
    • Victoria
      • Melbourne, Victoria, Australia, 3000
        • Peter MacCallum Cancer Centre-East Melbourne
      • Parkville, Victoria, Australia, 3050
        • Royal Melbourne Hospital
  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Hospital; Department of Med Oncology
    • Quebec
      • Montreal, Quebec, Canada, H3T 1E2
        • Jewish General Hospital
      • Montreal, Quebec, Canada, H2L 4M1
        • CHUM Hopital Notre-Dame
  • Germany
      • Dresden, Germany, 01307
        • Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden
      • Freiburg, Germany, 79106
        • Universitaetsklinikum Freiburg
  • Korea, Republic of
      • Seoul, Korea, Republic of, 03080
        • Seoul National University Hospital
      • Seoul, Korea, Republic of, 05505
        • Asan Medical Center - Oncology
  • Singapore
      • Singapore, Singapore, 119074
        • National University Hospital; Cancer Center
  • United States
    • California
      • Palo Alto, California, United States, 94304
        • Stanford University Medical Center
    • Colorado
      • Denver, Colorado, United States, 80220
        • Rocky Mountain Cancer Center - Denver
    • Connecticut
      • New Haven, Connecticut, United States, 06510
        • Yale University School Of Medicine
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Beth Israel Deaconess Med Ctr; Neurology/MS Center
      • Boston, Massachusetts, United States, 02114
        • Massachusets General Hospital Clinical Trial Network and Institute
    • New York
      • New York, New York, United States, 10065
        • Sloan Kettering Cancer Center; Pediatric Hematology/Oncology
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27514
        • UNC Lineberger Comprehensive Cancer Center
    • Oregon
      • Portland, Oregon, United States, 97225
        • Compass Oncology
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • SCRI-Tennessee Oncology
    • Texas
      • Arlington, Texas, United States, 76012
        • Texas Oncology, P.A.
    • Washington
      • Seattle, Washington, United States, 98195
        • University of Washington Seattle Cancer Care Alliance

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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:

Cancer-Specific 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

General Medical Exclusion Criteria:

  • 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

Exclusion Criteria Unique to Cobimetinib:

  • 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

Exclusion Criteria Related to Medications:

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
EXPERIMENTAL: 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.
Drug: Atezolizumab
Atezolizumab will be administered at a fixed dose as specified via IV infusion.
Other Names:
  • MPDL3280
Drug: Cobimetinib
Cobimetinib will be administered orally at an escalating dose during Stage 1 and at RP2D during Stage 2.
Other Names:
  • GDC-0973
EXPERIMENTAL: 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.
Drug: Atezolizumab
Atezolizumab will be administered at a fixed dose as specified via IV infusion.
Other Names:
  • MPDL3280
Drug: Cobimetinib
Cobimetinib will be administered orally at an escalating dose during Stage 1 and at RP2D during Stage 2.
Other Names:
  • GDC-0973

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Phase I: Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Time Frame: Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase
Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase
Phase I: Maximum Tolerated Dose of Cobimetinib
Time Frame: Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase
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
Time Frame: Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase
Day 15 to Day 42 of Cycle 1 (cycle length=42 days) of dose-escalation phase

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Percentage of Participants With Anti-Therapeutic Antibody (ATA) Response to Azetolizumab
Time Frame: 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)
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)
Time Frame: Baseline up to approximately 3.5 years
Baseline up to approximately 3.5 years
Serum Maximum Concentration (Cmax) of Atezolizumab
Time Frame: 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)
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
Time Frame: 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)
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
Time Frame: 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)
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)
Plasma Cmin of Cobimetinib
Time Frame: Pre-dose (Hour 0) on Day 29 of Cycle 1 (cycle length=42 days) and Day 15 of Cycle 2 (cycle length=28 days)
Pre-dose (Hour 0) on Day 29 of Cycle 1 (cycle length=42 days) and Day 15 of Cycle 2 (cycle length=28 days)
Area Under the Concentration-Time Curve (AUC) of Cobimetinib
Time Frame: 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)
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)
Percentage of Participants With Best Overall Response, as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time Frame: Baseline up to 3.5 years (detailed time frame is provided in the description)
Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 of Cycle 1 [cycle length=42 days]; thereafter every 12 weeks until progressive disease [PD] or death due to any cause, whichever occurs first [up to approximately 3.5 years])
Baseline up to 3.5 years (detailed time frame is provided in the description)
Percentage of Participants With Objective Response (OR; Confirmed Complete Response or Partial Response) as Assessed by Investigator Using RECIST v1.1
Time Frame: Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 Cycle 1 [cycle length=42 days]; thereafter every 12 weeks until PD or death due to any cause, whichever occurs first [up to approximately 3.5 years])
Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 Cycle 1 [cycle length=42 days]; thereafter every 12 weeks until PD or death due to any cause, whichever occurs first [up to approximately 3.5 years])
Duration of OR, as Determined by Investigator Using RECIST v1.1
Time Frame: Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 Cycle 1 [cycle length=42 days]; thereafter every 12 weeks until PD or death due to any cause, whichever occurs first [up to approximately 3.5 years])
Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 Cycle 1 [cycle length=42 days]; thereafter every 12 weeks until PD or death due to any cause, whichever occurs first [up to approximately 3.5 years])
Progression-Free Survival (PFS), as Determined by Investigator Using RECIST v1.1
Time Frame: Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 Cycle 1 [cycle length=42 days]; thereafter every 12 weeks until PD or death due to any cause, whichever occurs first [up to approximately 3.5 years])
Baseline up to 3.5 years (assessed at Baseline then every 8 weeks for the first 48 weeks following Day 1 Cycle 1 [cycle length=42 days]; thereafter every 12 weeks until PD or death due to any cause, whichever occurs first [up to approximately 3.5 years])
Overall Survival (OS)
Time Frame: Baseline up to death due to any cause (up to approximately 3.5 years)
Baseline up to death due to any cause (up to approximately 3.5 years)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Hoffmann-La Roche

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 27, 2013

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 4, 2019

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 4, 2019

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 14, 2013

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 14, 2013

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 20, 2013

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 17, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 16, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • GP28363
  • 2013-003329-27 (EUDRACT_NUMBER)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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