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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01988896
First received: November 14, 2013
Last updated: May 9, 2017
Last verified: May 2017
  Purpose
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.

Condition Intervention Phase
Solid Tumors Drug: Atezolizumab Drug: Cobimetinib Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase Ib Study of the Safety and Pharmacology of Atezolizumab Administered With Cobimetinib in Patients With Locally Advanced or Metastatic Solid Tumors

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • 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 ]
  • 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 ]
  • 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 ]

Secondary Outcome Measures:
  • 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) ]
  • Percentage of Participants With Adverse Events (AEs) or Serious AEs (SAEs) [ Time Frame: 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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) ]
  • 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])

  • 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]) ]
  • 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]) ]
  • 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]) ]
  • Overall Survival (OS) [ Time Frame: Baseline up to death due to any cause (up to approximately 3.5 years) ]

Enrollment: 153
Actual Study Start Date: December 27, 2013
Estimated Study Completion Date: April 23, 2018
Estimated Primary Completion Date: April 23, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: MPDL3280
Drug: Cobimetinib
Cobimetinib will be administered orally at an escalating dose during Stage 1 and at RP2D during Stage 2.
Other Name: 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 Name: MPDL3280
Drug: Cobimetinib
Cobimetinib will be administered orally at an escalating dose during Stage 1 and at RP2D during Stage 2.
Other Name: GDC-0973

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01988896

  Hide Study Locations
Locations
United States, California
Stanford University Medical Center
Stanford, California, United States, 94305
United States, Colorado
Rocky Mountain Cancer Center - Denver
Denver, Colorado, United States, 80220
United States, Connecticut
Yale University School Of Medicine
New Haven, Connecticut, United States, 06510
United States, Massachusetts
Massachusets General Hospital Clinical Trial Network and Institute
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Med Ctr; Neurology/MS Center
Boston, Massachusetts, United States, 02215
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02215
United States, New York
Sloan Kettering Cancer Center; Pediatric Hematology/Oncology
New York, New York, United States, 10065
United States, North Carolina
UNC Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States, 27514
United States, Tennessee
SCRI-Tennessee Oncology
Nashville, Tennessee, United States, 37203
United States, Texas
Texas Oncology, P.A.
Arlington, Texas, United States, 76012
Texas Oncology, P.A. - Tyler; Tyler Cancer Center
Tyler, Texas, United States, 75702
United States, Washington
University of Washington Seattle Cancer Care Alliance
Seattle, Washington, United States, 98195
Northwest Cancer Specialists - Vancouver
Vancouver, Washington, United States, 98684
Australia, Victoria
Peter MacCallum Cancer Centre-East Melbourne
Melbourne, Victoria, Australia, 3000
Canada, Ontario
Princess Margaret Hospital; Department of Med Oncology
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Jewish General Hospital
Montreal, Quebec, Canada, H3T 1E2
CHUM Hôpital Notre-Dame
Montréall, Quebec, Canada, H2L 4M1
Germany
Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden
Dresden, Germany, 01307
Universitaetsklinikum Freiburg
Freiburg, Germany, 79106
Korea, Republic of
Seoul National University Hospital
Seoul, Korea, Republic of, 03080
Asan Medical Center
Seoul, Korea, Republic of, 05505
Singapore
National University Hospital; Investigational Medicine Unit
Singapore, Singapore, 119074
Raffles Hospital
Singapore, Singapore, 188770
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01988896     History of Changes
Other Study ID Numbers: GP28363
2013-003329-27 ( EudraCT Number )
Study First Received: November 14, 2013
Last Updated: May 9, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on June 29, 2017