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

November 14, 2013
March 3, 2016
December 2013
October 2017   (final data collection date for primary outcome measure)
Percentage of Participants with Dose-Limiting Toxicity (DLT) [ Time Frame: Day 1 to Day 28 ] [ Designated as safety issue: Yes ]
  • Safety: Incidence of dose-limiting toxicities (DLT) [ Time Frame: 28 days following start of combination treatment ] [ Designated as safety issue: Yes ]
  • Safety: Incidence of adverse events (AE) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT01988896 on ClinicalTrials.gov Archive Site
  • 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 ]
  • Pharmacokinetics: Maximum concentration (Cmax) of MPDL3280A [ Time Frame: Approximately 1 year ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Plasma Cmax of Cobimetinib [ Time Frame: Approximately 1 year ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Study of Atezolizumab in Combination With Cobimetinib in Participants With Locally Advanced or Metastatic Solid Tumors
A Phase 1b Study of the Safety and Pharmacology of Atezolizumab Administered With Cobimetinib in Patients With Locally Advanced or Metastatic Solid Tumors
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.
Not Provided
Interventional
Phase 1
Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Solid Tumors
  • Drug: Atezolizumab
    Administered via IV infusion.
    Other Name: MPDL3280
  • Drug: Cobimetinib
    Administered via oral tablets.
    Other Name: GDC-0973
  • 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.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Cobimetinib
  • Experimental: Dose-expansion: cobimetinib + atezolizumab
    Participants will receive atezolizumab at doses determined during dose-escalation stage.
    Interventions:
    • Drug: Atezolizumab
    • Drug: Cobimetinib
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
151
October 2017
October 2017   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
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
United States,   Australia,   Canada,   Germany,   Korea, Republic of,   Singapore
Czech Republic,   France,   Spain,   Sweden,   United Kingdom
 
NCT01988896
GP28363, 2013-003329-27
Not Provided
Not Provided
Not Provided
Hoffmann-La Roche
Hoffmann-La Roche
Not Provided
Study Director: Clinical Trials Hoffmann-La Roche
Hoffmann-La Roche
March 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP