Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

A Phase 1b Study of Atezolizumab in Combination With Vemurafenib or Vemurafenib Plus Cobimetinib in Participants With BRAFV600-Mutation Positive Metastatic Melanoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2016 by Genentech, Inc.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01656642
First received: August 1, 2012
Last updated: September 1, 2016
Last verified: September 2016
  Purpose
This is an open-label, multicenter, Phase Ib, dose-escalation and cohort-expansion study of atezolizumab (anti-PD-L1 antibody) in combination with vemurafenib or vemurafenib plus cobimetinib in 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 [TECENTRIQ]
Drug: Cobimetinib
Drug: Vemurafenib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase Ib, Open-Label Study of The Safety and Pharmacology of Atezolizumab (Anti PD-L1 Antibody) Administered in Combination With Vemurafenib or Vemurafenib Plus Cobimetinib in Patients With BRAFV600-Mutation Positive Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by Genentech, Inc.:

Primary Outcome Measures:
  • Percentage of Participants With Dose Limiting Toxicities (DLT) [ Time Frame: 21 days (or 28 days for Cohort 4) following the first administration of atezolizumab ] [ Designated as safety issue: Yes ]
  • Percentage of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: up to approximately 6 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Area Under the Concentration-Time Curve (AUC) of Atezolizumab [ Time Frame: pre-dose, 30 minutes post-dose on Day 1 of Cycle 1 and 2, pre-dose on Day 15 and Day 8 of Cycle 1, pre-dose on Day 1 of Cycle 3, 4, 5, 7, 8 and every 8 cycles thereafter up to 90 days following the end of treatment visit (up to approximately 6 years) ] [ Designated as safety issue: No ]
  • Maximum Serum Concentration (Cmax) of Atezolizumab [ Time Frame: pre-dose, 30 minutes post-dose on Day 1 of Cycle 1 and 2, pre-dose on Day 15 and Day 8 of Cycle 1, pre-dose on Day 1 of Cycle 3, 4, 5, 7, 8 and every 8 cycles thereafter up to 90 days following the end of treatment visit (up to approximately 6 years) ] [ Designated as safety issue: No ]
  • Minimum Observed Serum Trough Concentration (Cmin) of Atezolizumab [ Time Frame: pre-dose on Day 1 of Cycle 1 and 2, pre-dose on Day 15 and Day 8 of Cycle 1, pre-dose on Day 1 of Cycle 3, 4, 5, 7, 8 and every 8 cycles thereafter up to 90 days following the end of treatment visit (up to approximately 6 years) ] [ Designated as safety issue: No ]
  • Maximum Plasma Concentration (Cmax) of Vemurafenib [ Time Frame: run-in period: pre-dose on Day 1, 8, and 22, 3 hours post-dose on Day 22; combination treatment period: pre-dose on Day 1 of Cycle 1 and 2, 3 hours post-dose on Day 1 of Cycle 2 ] [ Designated as safety issue: No ]
  • Minimum Observed Plasma Trough Concentration (Cmin) of Vemurafenib [ Time Frame: run-in period: pre-dose on Day 1, 8, and 22; combination treatment period: pre-dose on Day 1 of Cycle 1 and 2 ] [ Designated as safety issue: No ]
  • Maximum Plasma Concentration (Cmax) of Cobimetinib [ Time Frame: run-in period: pre-dose on Day 1, 8, and 22; combination treatment period: pre-dose on Day 1 and 15 of Cycle 1 and Day 15 of Cycle 2, 3 hours post-dose on Day 15 of Cycle 1 ] [ Designated as safety issue: No ]
  • Minimum Observed Plasma Trough Concentration (Cmin) of Cobimetinib [ Time Frame: run-in period: pre-dose on Day 1, 8, and 22; combination treatment period: pre-dose on Day 1 and 15 of Cycle 1 and Day 15 of Cycle 2 ] [ Designated as safety issue: No ]
  • Percentage of Participants With Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Baseline until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks of combination treatment period for first 24 weeks and then every 9 weeks up to approximately 6 years) ] [ Designated as safety issue: No ]
  • Percentage of Participants with Objective Response According to Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Baseline until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks of combination treatment period for first 24 weeks and then every 9 weeks up to approximately 6 years) ] [ Designated as safety issue: No ]
  • Duration of Objective Response According to RECIST [ Time Frame: Baseline until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks of combination treatment period for first 24 weeks and then every 9 weeks up to approximately 6 years) ] [ Designated as safety issue: No ]
  • Overall Survival (OS) Duration [ Time Frame: Baseline until death up to 6 years ] [ Designated as safety issue: No ]
  • Progression Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: Baseline until disease progression or death, whichever occurred first (assessed at baseline, every 6 weeks of combination treatment period for first 24 weeks and then every 9 weeks up to approximately 6 years) ] [ Designated as safety issue: No ]
  • Mean Atezolizumab Dose [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]
  • Percentage of Participants With Anti-Atezolizumab Antibodies [ Time Frame: pre-dose on Day 1 (run-in period), pre-dose on Day 1 of Cycle 2, 3, 4 and 8, and every 8 cycles thereafter up to 90 days following the end of treatment visit (up to approximately 6 years) ] [ Designated as safety issue: No ]
  • Total Number of Atezolizumab Cycles [ Time Frame: approximately 12 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 70
Study Start Date: August 2012
Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: C1: Ate+ Vem - No Run-in
Cohort 1 (C1): Participants will receive atezolizumab (Ate) 1200 milligrams (mg) every 3 weeks (q3w) along with vemurafenib (Vem) 750 mg QD for 21 days in each cycle followed by 7 days off treatment (28-day cycle). Treatment will continue until disease progression, unacceptable toxicity, or withdrawal of consent occurs.
Drug: Atezolizumab [TECENTRIQ]
Atezolizumab will be administered every 3 weeks (q3w) or every 2 weeks (q2w).
Other Name: MPDL3280A, an engineered anti-PD-L1 antibody
Drug: Vemurafenib
Oral repeating dose, depending on arm/cohort
Other Name: Zelboraf
Experimental: C2: Ate + Vem (56 Day Run-in)
Run-in period (56 days): participants will receive vemurafenib 960 mg orally twice daily from day 1 to 49 and vemurafenib 720 mg orally twice daily from day 50 to 56. Combination treatment period: Participants will receive fixed dose of atezolizumab 1200 mg IV q3w in combination with vemurafenib 720 mg orally twice daily in 21 days cycle.
Drug: Atezolizumab [TECENTRIQ]
Atezolizumab will be administered every 3 weeks (q3w) or every 2 weeks (q2w).
Other Name: MPDL3280A, an engineered anti-PD-L1 antibody
Drug: Vemurafenib
Oral repeating dose, depending on arm/cohort
Other Name: Zelboraf
Experimental: C3: Ate + Vem (28 Day Run-in)
Run-in period (28 days): participants will receive vemurafenib 960 mg orally twice daily for 21 days, then vemurafenib 720 mg orally twice daily for 7 days. Combination treatment period: Participants will receive fixed dose of atezolizumab 1200 mg IV q3w in combination with vemurafenib 720 mg orally twice daily in 21 days cycle.
Drug: Atezolizumab [TECENTRIQ]
Atezolizumab will be administered every 3 weeks (q3w) or every 2 weeks (q2w).
Other Name: MPDL3280A, an engineered anti-PD-L1 antibody
Drug: Vemurafenib
Oral repeating dose, depending on arm/cohort
Other Name: Zelboraf
Experimental: C4: Ate + Vem + Cob (28 Day Run-in)
Run-in period (28 days): participants will receive vemurafenib 960 mg orally twice daily for 21 days, then vemurafenib 720 mg orally twice daily for 7 days in combination with cobimetinib (Cob) 60 mg IV once daily, 21 days on/7 days off schedule (21/7). Combination treatment period: Participants will receive fixed dose of atezolizumab 800 mg IV q2w in combination with vemurafenib 720 mg orally twice daily and cobimetinib 60 mg orally once daily 21/7 in 28 days cycle.
Drug: Atezolizumab [TECENTRIQ]
Atezolizumab will be administered every 3 weeks (q3w) or every 2 weeks (q2w).
Other Name: MPDL3280A, an engineered anti-PD-L1 antibody
Drug: Cobimetinib
Oral repeating dose
Other Name: GDC-0973; XL518, Cotellic
Drug: Vemurafenib
Oral repeating dose, depending on arm/cohort
Other Name: Zelboraf
Experimental: ECA: Ate + Vem + Cob (Mandatory Biopsy PD)
Expansion cohort A (ECA): Approximately 10 participants who experienced disease progression (PD) after receiving prior checkpoint inhibitor therapy will be enrolled and treated with atezolizumab + vemurafenib + cobimetinib. Serial biopsy tissue sample collections of accessible lesions will be mandatory for all participants enrolled in this cohort. The doses will be decided based on the results of Cohorts 1-4.
Drug: Atezolizumab [TECENTRIQ]
Atezolizumab will be administered every 3 weeks (q3w) or every 2 weeks (q2w).
Other Name: MPDL3280A, an engineered anti-PD-L1 antibody
Drug: Cobimetinib
Oral repeating dose
Other Name: GDC-0973; XL518, Cotellic
Drug: Vemurafenib
Oral repeating dose, depending on arm/cohort
Other Name: Zelboraf
Experimental: ECB: Ate + Vem + Cob (Mandatory Biopsy)
Approximately 20 participants will be enrolled and treated with atezolizumab + vemurafenib + cobimetinib. Serial biopsy tissue sample collections of accessible lesions will be mandatory for all participants. The doses will be decided based on the results of Cohorts 1-4.
Drug: Atezolizumab [TECENTRIQ]
Atezolizumab will be administered every 3 weeks (q3w) or every 2 weeks (q2w).
Other Name: MPDL3280A, an engineered anti-PD-L1 antibody
Drug: Cobimetinib
Oral repeating dose
Other Name: GDC-0973; XL518, Cotellic
Drug: Vemurafenib
Oral repeating dose, depending on arm/cohort
Other Name: Zelboraf
Experimental: ECC: Ate + Vem + Cob (No Mandatory Biopsy)
Approximately 10 participants who experienced disease progression after receiving prior checkpoint inhibitor therapy will be enrolled and treated with atezolizumab + vemurafenib + cobimetinib. Serial biopsy tissue sample collections will be optional for all participants enrolled in this cohort. The doses will be decided based on the results of Cohorts 1-4.
Drug: Atezolizumab [TECENTRIQ]
Atezolizumab will be administered every 3 weeks (q3w) or every 2 weeks (q2w).
Other Name: MPDL3280A, an engineered anti-PD-L1 antibody
Drug: Cobimetinib
Oral repeating dose
Other Name: GDC-0973; XL518, Cotellic
Drug: Vemurafenib
Oral repeating dose, depending on arm/cohort
Other Name: Zelboraf

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
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 (this exclusion criterion does not apply to patients enrolled in Expansion Cohort A)
  • 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
  • Any active malignancy (other than BRAF-mutated melanoma) or a previous malignancy within the past 3 years
  • 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
  • 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
  • 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. and Canada) 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
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

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: September 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
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 28, 2016