A Phase 1b Study of Atezolizumab (MPDL3280A, Anti-PD-L1 Antibody) in Combination With Vemurafenib or Vemurafenib Plus Cobimetinib in Participants With Previously Untreated BRAFV600-Mutation Positive Metastatic Melanoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2016 by Genentech, Inc.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01656642
First received: August 1, 2012
Last updated: February 1, 2016
Last verified: February 2016
  Purpose
This is an open-label, multicenter, Phase Ib, dose-escalation and cohort-expansion study of atezolizumab (MPDL3280A) in combination with vemurafenib or vemurafenib plus cobimetinib in previously untreated participants with BRAFV600-mutation positive metastatic melanoma. Enrolled participants may continue treatment until they are no longer experiencing clinical benefit as assessed by the investigator and in alignment with the protocol.

Condition Intervention Phase
Malignant Melanoma
Drug: Atezolizumab
Drug: Cobimetinib
Drug: Vemurafenib
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 Ib, Open-Label Study of The Safety and Pharmacology of MPDL3280A Administered in Combination With Vemurafenib or Vemurafenib Plus Cobimetinib in Patients With Previously Untreated BRAFV600-Mutation Positive Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Incidence of dose-limiting toxicities (DLTs) [ Time Frame: Timeframe: 21 days (or 28 days for Cohort 4) following the first administration of atezolizumab ] [ Designated as safety issue: No ]
  • Nature of dose-limiting toxicities (DLTs) [ Time Frame: Timeframe: 21 days (or 28 days for Cohort 4) following the first administration of atezolizumab ] [ Designated as safety issue: No ]
  • Incidence of adverse events and laboratory abnormalities graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0 [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]
  • Nature of adverse events and laboratory abnormalities graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0 [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]
  • Severity of adverse events and laboratory abnormalities graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), Version 4.0 [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Incidence of anti-atezolizumab antibodies [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]
  • Change in vital signs, including electrocardiograms (ECGs) [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]
  • Change in clinical laboratory results [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]
  • Number of cycles and dose intensity of each component of the treatment regimen [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 55
Study Start Date: August 2012
Estimated Study Completion Date: June 2018
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1
Atezolizumab (MPDL3280A) + vemurafenib
Drug: Atezolizumab
Intravenous administration, fixed at either 15 or 20 milligram per kilogram (mg/kg) every 3 weeks (q3w), or a fixed dose of either 1200 mg q3w, or 800 mg every 2 weeks (q2w), depending on the arm/cohort. Participants currently in Cohorts 2 and 3 still receiving atezolizumab (MPDL3280A) therapy (and any participants enrolled after updated formulation availability) will be switched to receive a fixed dose of 1200 mg or 800 mg of atezolizumab formulation.
Other Name: MPDL3280A
Drug: Vemurafenib
Oral repeating dose, depending on arm/cohort
Experimental: Cohort 2
Atezolizumab + vemurafenib
Drug: Atezolizumab
Intravenous administration, fixed at either 15 or 20 milligram per kilogram (mg/kg) every 3 weeks (q3w), or a fixed dose of either 1200 mg q3w, or 800 mg every 2 weeks (q2w), depending on the arm/cohort. Participants currently in Cohorts 2 and 3 still receiving atezolizumab (MPDL3280A) therapy (and any participants enrolled after updated formulation availability) will be switched to receive a fixed dose of 1200 mg or 800 mg of atezolizumab formulation.
Other Name: MPDL3280A
Drug: Vemurafenib
Oral repeating dose, depending on arm/cohort
Experimental: Cohort 3
Atezolizumab + vemurafenib
Drug: Atezolizumab
Intravenous administration, fixed at either 15 or 20 milligram per kilogram (mg/kg) every 3 weeks (q3w), or a fixed dose of either 1200 mg q3w, or 800 mg every 2 weeks (q2w), depending on the arm/cohort. Participants currently in Cohorts 2 and 3 still receiving atezolizumab (MPDL3280A) therapy (and any participants enrolled after updated formulation availability) will be switched to receive a fixed dose of 1200 mg or 800 mg of atezolizumab formulation.
Other Name: MPDL3280A
Drug: Vemurafenib
Oral repeating dose, depending on arm/cohort
Experimental: Cohort 4
Atezolizumab + vemurafenib + cobimetinib
Drug: Atezolizumab
Intravenous administration, fixed at either 15 or 20 milligram per kilogram (mg/kg) every 3 weeks (q3w), or a fixed dose of either 1200 mg q3w, or 800 mg every 2 weeks (q2w), depending on the arm/cohort. Participants currently in Cohorts 2 and 3 still receiving atezolizumab (MPDL3280A) therapy (and any participants enrolled after updated formulation availability) will be switched to receive a fixed dose of 1200 mg or 800 mg of atezolizumab formulation.
Other Name: MPDL3280A
Drug: Cobimetinib
Oral repeating dose
Other Name: GDC-0973; XL518
Drug: Vemurafenib
Oral repeating dose, depending on arm/cohort
Experimental: Expansion Cohort A
Atezolizumab + vemurafenib. Up to 10 additional participants. Mandatory biopsies.
Drug: Atezolizumab
Intravenous administration, fixed at either 15 or 20 milligram per kilogram (mg/kg) every 3 weeks (q3w), or a fixed dose of either 1200 mg q3w, or 800 mg every 2 weeks (q2w), depending on the arm/cohort. Participants currently in Cohorts 2 and 3 still receiving atezolizumab (MPDL3280A) therapy (and any participants enrolled after updated formulation availability) will be switched to receive a fixed dose of 1200 mg or 800 mg of atezolizumab formulation.
Other Name: MPDL3280A
Drug: Vemurafenib
Oral repeating dose, depending on arm/cohort
Experimental: Expansion Cohort B
Atezolizumab + vemurafenib + cobimetinib. Up to 20 additional participants. Mandatory biopsies.
Drug: Atezolizumab
Intravenous administration, fixed at either 15 or 20 milligram per kilogram (mg/kg) every 3 weeks (q3w), or a fixed dose of either 1200 mg q3w, or 800 mg every 2 weeks (q2w), depending on the arm/cohort. Participants currently in Cohorts 2 and 3 still receiving atezolizumab (MPDL3280A) therapy (and any participants enrolled after updated formulation availability) will be switched to receive a fixed dose of 1200 mg or 800 mg of atezolizumab formulation.
Other Name: MPDL3280A
Drug: Cobimetinib
Oral repeating dose
Other Name: GDC-0973; XL518
Drug: Vemurafenib
Oral repeating dose, depending on arm/cohort

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologic or cytologic documentation of metastatic or Stage IIIc unresectable melanoma, with BRAFV600 mutation as assessed by BRAF V600 Mutation Test. Origin of the primary tumor may be of skin, mucosal, or acral locations but not of uveal origin. Participants having an unknown primary tumor may be eligible if uveal melanoma can be ruled out
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Adequate hematologic and end organ function
  • Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
  • For women of childbearing potential, agreement to remain abstinent (refrain from heterosexual intercourse) or use 2 effective forms of contraceptive methods including at least 1 that results in a failure rate of less than (<) 1 percent (%) per year during the treatment period and for at least 6 months after the last dose of study drug
  • For men, agreement to remain abstinent (refrain from heterosexual intercourse) or use 2 contraceptive measures, and agreement to refrain from donating sperm
  • Agreement to mandatory archival tissue or fresh biopsy
  • Agreement to the collection of serial fresh lesion samples (required, if feasible, for entry into Escalation Cohorts 4 and expansion cohorts and optional, but encouraged in Escalation Cohorts 2 & 3)

Exclusion Criteria:

  • Receipt of prior systemic anti-cancer therapy for unresectable, locally advanced or metastatic melanoma
  • Receipt of prior immunomodulatory agents, including programmed death-1 (PD)-1 or programmed death-ligand 1 (PD-L1) targeted therapy or cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) targeted therapy, including ipilimumab
  • Receipt of prior mitogen-activated protein kinase (MAPK) inhibitor pathway agents, including mitogen-activated protein kinase (MEK) kinase inhibitor and BRAF kinase inhibitor
  • Major surgical procedure within 28 days prior to Day 1 or anticipation of need for a major surgical procedure during the course of the study
  • Radiotherapy less than or equal to (<=) 7 days prior to Day 1
  • Adverse events from prior anti-cancer therapy that have not resolved to Grade <= 1 except for alopecia
  • Current severe, uncontrolled systemic disease excluding cancer
  • Known clinically significant liver disease
  • Active or untreated central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior assessments for CNS metastases
  • Any active malignancy (other than BRAF-mutated melanoma) or a previous malignancy within the past 3 years
  • Prior allogeneic bone marrow transplantation or prior solid organ transplantation
  • History of autoimmune disease
  • History of idiopathic pulmonary fibrosis, risk of pulmonary toxicity, or evidence of active pneumonitis on screening chest CT scan
  • History of human immunodeficiency virus (HIV) infection
  • Participants with active hepatitis B or active hepatitis C
  • Active tuberculosis
  • Infections within 4 weeks prior to Day 1 or signs or symptoms of infection within 2 weeks prior to Day 1
  • Received oral or intravenous antibiotics within 2 weeks prior to Day 1
  • Administration of a live, attenuated vaccine within 4 weeks before Day 1 or anticipation that such a live attenuated vaccine will be required during the study
  • History of clinically significant cardiac or pulmonary dysfunction
  • For participants to be enrolled into the vemurafenib+cobimetinib+ atezolizumab cohorts: history of or evidence of retinal pathology on ophthalmologic examination that is considered a risk factor for neurosensory retinal detachment/central serous chorioretinopathy, retinal vein occlusion, or neovascular macular degeneration
  • Treatment with systemic immunosuppressive medications within 4 weeks prior to Cycle 1, Day 1
  • Bisphosphonate therapy for symptomatic hypercalcemia
  • Pregnant or breastfeeding women
  • Intake of St. John's wort or hyperforin (potent cytochrome P450 CYP3A4 enzyme inducer) or grapefruit juice (potent cytochrome P450 CYP3A4 enzyme inhibitor) within 7 days prior to initiation of study treatment
  • Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation or known hypersensitivity to any component of cobimetinib or vemurafenib
  • History of malabsorption or other clinically significant metabolic dysfunction that may interfere with absorption of oral study treatment
  • Inability or unwillingness to swallow pills
  • Any other diseases, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the participant at high risk from treatment complications
  • Inability to comply with study and follow-up procedures
  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: NCT01656642

Contacts
Contact: Reference Study ID Number: GP28384 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. Only) global.rochegenentechtrials@roche.com

Locations
United States, California
Recruiting
Los Angeles, California, United States, 90024
Recruiting
Los Angeles, California, United States, 90025
United States, Colorado
Recruiting
Aurora, Colorado, United States, 80045
United States, Florida
Recruiting
Sarasota, Florida, United States, 34232
Not yet recruiting
West Palm Beach, Florida, United States, 33401
United States, Massachusetts
Recruiting
Boston, Massachusetts, United States, 02114
Recruiting
Boston, Massachusetts, United States, 02215
Terminated
Boston, Massachusetts, United States, 02215
United States, Tennessee
Recruiting
Nashville, Tennessee, United States, 37203
United States, Texas
Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
Genentech, Inc.
Investigators
Study Director: Clinical Trials Genentech, Inc.
  More Information

No publications provided by Genentech, Inc.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT01656642     History of Changes
Other Study ID Numbers: GP28384  2012-002738-35 
Study First Received: August 1, 2012
Last Updated: February 1, 2016
Health Authority: United States: Food and Drug Administration

Keywords provided by Genentech, Inc.:
PD-L1
PD-1
PDL1
antiPD-L1
MPDL3280A
Melanoma
BRAF
MPDL320A

Additional relevant MeSH terms:
Melanoma
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Germ Cell and Embryonal
Neoplasms, Nerve Tissue
Neuroectodermal Tumors
Neuroendocrine Tumors
Nevi and Melanomas

ClinicalTrials.gov processed this record on February 11, 2016