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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2016 by Hoffmann-La Roche
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01988896
First received: November 14, 2013
Last updated: March 3, 2016
Last verified: March 2016
  Purpose
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
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase 1b 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:
  • Percentage of Participants with Dose-Limiting Toxicity (DLT) [ Time Frame: Day 1 to Day 28 ] [ Designated as safety issue: Yes ]

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 and at treatment completion visit (up to approximately 3.5 years) ] [ Designated as safety issue: No ]
  • Duration of Objective Response [ Time Frame: Screening and thereafter every 8 weeks until disease progression or death or end of study, whichever occurred first (up to approximately 3.5 years) ] [ Designated as safety issue: No ]
  • Percentage of Participants with Adverse Events (AEs) or Serious AEs (SAEs) [ Time Frame: up to approximately 3.5 years ] [ Designated as safety issue: No ]
  • Maximum Serum Concentration (Cmax) of Atezolizumab [ Time Frame: Pre-infusion (Hour 0), 30 minutes post infusion on Cycle 1 Day 1, pre-infusion (Hour 0) on Day 1 of Cycles 2, 3, 4, 8 and at treatment completion visit (up to approximately 3.5 years) ] [ Designated as safety issue: No ]
  • Minimum Serum Concentration (Cmin) of Atezolizumab [ Time Frame: Pre-infusion (Hour 0) on Day 1 of Cycles 1, 2, 3, 4, 8, and at treatment completion visit (up to approximately 3.5 years) ] [ Designated as safety issue: No ]
  • Cmax of Cobimetinib [ Time Frame: Pre-dose (Hour 0), 2, 4, 6 hours post-dose on Cycle 1 Day 29, pre-dose (Hour 0), 2, 4, 6 hours post-dose on Cycle 2 Day 15\n\n ] [ Designated as safety issue: No ]
  • Cmin of Cobimetinib [ Time Frame: Pre-dose (Hour 0), 2, 4, 6 hours post-dose on Cycle 1 Day 29, pre-dose (Hour 0), 2, 4, 6 hours post-dose on Cycle 2 Day 15\n ] [ Designated as safety issue: No ]
  • Percentage of Participants with Best Overall Response According to RECIST v.1.1 [ Time Frame: Screening and thereafter every 8 weeks until disease progression or death or end of study, whichever occurred first (up to approximately 3.5 years) ] [ Designated as safety issue: No ]
  • Percentage of Participants with Objective Response (Complete Response or Partial Response) According to RECIST v1.1 [ Time Frame: Screening and thereafter every 8 weeks until disease progression or death or end of study, whichever occurred first (up to approximately 3.5 years) ] [ Designated as safety issue: No ]
  • Duration of Progression-Free Survival [ Time Frame: Screening and thereafter every 8 weeks until disease progression or death or end of study, whichever occurred first (up to approximately 3.5 years) ] [ Designated as safety issue: No ]
  • Duration of Overall Survival [ Time Frame: Screening and thereafter every 8 weeks until disease progression or death or end of study, whichever occurred first (up to approximately 3.5 years) ] [ Designated as safety issue: No ]

Estimated Enrollment: 151
Study Start Date: December 2013
Estimated Study Completion Date: October 2017
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dose-escalation: cobimetinib + atezolizumab
Participants will receive 800 milligrams (mg) of atezolizumab IV every 2 weeks and cobimetinib at a starting dose of 20 mg once daily for 21 consecutive days followed by 7 days off drug in each 28-day cycle. Cobimetinib doses will be escalated until a combination maximum tolerated dose is defined.
Drug: Atezolizumab
Administered via IV infusion.
Other Name: MPDL3280
Drug: Cobimetinib
Administered via oral tablets.
Other Name: GDC-0973
Experimental: Dose-expansion: cobimetinib + atezolizumab
Participants will receive atezolizumab at doses determined during dose-escalation stage.
Drug: Atezolizumab
Administered via IV infusion.
Other Name: MPDL3280
Drug: Cobimetinib
Administered via oral tablets.
Other Name: GDC-0973

  Eligibility

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

Inclusion Criteria:

  • Signed Informed Consent Form.
  • 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 Response Evaluation Criteria in Solid Tumors (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.
  • Consent to undergo pre-treatment and/or on-treatment tumor biopsies for biomarker analysis for participants in biopsy-mandated cohorts.

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 Chinese hamster ovary cell products.
  • Allergy or hypersensitivity to components 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) >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 (CD137) 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

Contacts
Contact: Reference Study ID Number: GP28363 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global.rochegenentechtrials@roche.com

  Show 23 Study Locations
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 
Study First Received: November 14, 2013
Last Updated: March 3, 2016
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on September 26, 2016