We updated the design of this site on September 25th. Learn more.
Show more
ClinicalTrials.gov
ClinicalTrials.gov Menu

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 ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01656642
First Posted: August 3, 2012
Last Update Posted: August 16, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Genentech, Inc.
  Purpose
This is an open-label, multicenter, Phase Ib, dose-escalation and cohort-expansion study of atezolizumab (anti-programmed death-ligand 1 [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 Drug: Cobimetinib Drug: Vemurafenib Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (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 [ Time Frame: 21 days (or 28 days for Cohort 4) following the first administration of atezolizumab ]
  • Percentage of Participants With Adverse Events [ Time Frame: Baseline up to approximately 6 years ]

Secondary Outcome Measures:
  • Area Under the Concentration-Time Curve (AUC) of Atezolizumab [ Time Frame: Predose (0 hour), 30 minutes postdose on Day (D) 1 of Cycles (C) 1, 2; predose on D15, D8 of C1; predose on D1 of C3, 4, 5, 7, 8, every 8 cycles thereafter up to 90 days after end of treatment visit (up to approximately 6 years) (Cycle=28 days) ]
  • Maximum Serum Concentration of Atezolizumab [ Time Frame: Predose (0 hour), 30 minutes postdose on Day (D) 1 of Cycles (C) 1, 2; predose on D15, D8 of C1; predose on D1 of C3, 4, 5, 7, 8, every 8 cycles thereafter up to 90 days after end of treatment visit (up to approximately 6 years) (Cycle=28 days) ]
  • Maximum Plasma Concentration of Vemurafenib [ Time Frame: Run-in period: predose (0 hour) on D1, 8, and 22, 3 hours postdose on D22; combination treatment period: predose (0 hour) on D1 of C1 and 2, 3 hours postdose on D1 of C2 (Cycle = 28 days) ]
  • Minimum Observed Plasma Trough Concentration (Cmin) of Vemurafenib [ Time Frame: Run-in period: predose (0 hour) on D1, 8, and 22; combination treatment period: predose (0 hour) on D1 of C1 and 2 (Cycle = 28 days) ]
  • Maximum Plasma Concentration of Cobimetinib [ Time Frame: Run-in period: predose (0 hour) on D1, 8, and 22; combination treatment period: predose (0 hour) on D1 and 15 of C1 and D15 of C2, 3 hours postdose on D15 of Cycle 1 (Cycle = 28 days) ]
  • Cmin of Cobimetinib [ Time Frame: Run-in period: predose (0 hour) on D1, 8, and 22; combination treatment period: predose (0 hour) on D1 and 15 of C1 and D15 of C2 (Cycle = 28 days) ]
  • Percentage of Participants With Best Overall Response According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) [ 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) ]
  • Percentage of Participants with Objective Response According to RECIST v1.1 [ 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) ]
  • Percentage of Participants with Objective Response According to Immune-Related Response Criteria (irRC) [ 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) ]
  • Duration of Objective Response According to RECIST v1.1 [ 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) ]
  • Duration of Objective Response According to irRC [ 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) ]
  • Progression Free Survival According to RECIST v1.1 [ 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) ]
  • Progression Free Survival According to irRC [ 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) ]
  • Overall Survival Duration [ Time Frame: Baseline until death up to 6 years ]
  • Mean Atezolizumab Dose [ Time Frame: Approximately 12 months ]
  • Total Number of Atezolizumab Cycles [ Time Frame: Approximately 12 months ]
  • Percentage of Participants With Anti-Atezolizumab Antibodies [ Time Frame: Predose (0 hour) on D1 (run-in period), predose (0 hour) on D1 of C2, 3, 4, 8, every 8 cycles thereafter up to 90 days after end of treatment visit (up to approximately 6 years) (Cycle=28 days) ]

Enrollment: 67
Actual Study Start Date: August 13, 2012
Estimated Study Completion Date: November 28, 2018
Estimated Primary Completion Date: November 28, 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Cohort 1 (C1): Ate+Vem - No Run-in
Participants will receive atezolizumab (Ate) 1200 milligrams (mg) every 3 weeks (q3w) along with vemurafenib (Vem) 720 mg twice daily (BID) 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
Atezolizumab will be administered q3w or q2w.
Other Names:
  • MPDL3280A, an engineered anti-PD-L1 antibody
  • TECENTRIQ
  • RO5541267
Drug: Vemurafenib
Oral repeating dose, depending on arm/cohort
Other Names:
  • Zelboraf
  • RO5185426
Experimental: Cohort 2 (C2): Ate+Vem (56 Day Run-in)
Run-in period (56 days): participants will receive vemurafenib 960 mg orally BID from Day 1 to 49 and vemurafenib 720 mg orally BID from Day 50 to 56. Combination treatment period: Participants will receive fixed dose of atezolizumab 1200 mg intravenous (IV) q3w in combination with vemurafenib 720 mg orally BID in 21 days cycle.
Drug: Atezolizumab
Atezolizumab will be administered q3w or q2w.
Other Names:
  • MPDL3280A, an engineered anti-PD-L1 antibody
  • TECENTRIQ
  • RO5541267
Drug: Vemurafenib
Oral repeating dose, depending on arm/cohort
Other Names:
  • Zelboraf
  • RO5185426
Experimental: Cohort 3 (C3): Ate+Vem (28 Day Run-in)
Run-in period (28 days): participants will receive vemurafenib 960 mg orally BID for 21 days, then vemurafenib 720 mg orally BID for 7 days. Combination treatment period: Participants will receive fixed dose of atezolizumab 1200 mg IV q3w in combination with vemurafenib 720 mg orally BID in 21 days cycle.
Drug: Atezolizumab
Atezolizumab will be administered q3w or q2w.
Other Names:
  • MPDL3280A, an engineered anti-PD-L1 antibody
  • TECENTRIQ
  • RO5541267
Drug: Vemurafenib
Oral repeating dose, depending on arm/cohort
Other Names:
  • Zelboraf
  • RO5185426
Experimental: Cohort 4 (C4): Ate+Vem+Cob (28 Day Run-in)
Run-in period (28 days): participants will receive vemurafenib 960 mg orally BID for 21 days, then vemurafenib 720 mg orally BID 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 every 2 weeks (q2w) in combination with vemurafenib 720 mg orally BID and cobimetinib 60 mg orally once daily 21/7 in 28 days cycle.
Drug: Atezolizumab
Atezolizumab will be administered q3w or q2w.
Other Names:
  • MPDL3280A, an engineered anti-PD-L1 antibody
  • TECENTRIQ
  • RO5541267
Drug: Cobimetinib
Oral repeating dose
Other Names:
  • GDC-0973
  • XL518
  • Cotellic
  • RO5514041
Drug: Vemurafenib
Oral repeating dose, depending on arm/cohort
Other Names:
  • Zelboraf
  • RO5185426
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 plus (+) 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
Atezolizumab will be administered q3w or q2w.
Other Names:
  • MPDL3280A, an engineered anti-PD-L1 antibody
  • TECENTRIQ
  • RO5541267
Drug: Cobimetinib
Oral repeating dose
Other Names:
  • GDC-0973
  • XL518
  • Cotellic
  • RO5514041
Drug: Vemurafenib
Oral repeating dose, depending on arm/cohort
Other Names:
  • Zelboraf
  • RO5185426
Experimental: ECB: Ate+Vem+Cob (Mandatory Biopsy)
Expansion Cohort B (ECB): 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
Atezolizumab will be administered q3w or q2w.
Other Names:
  • MPDL3280A, an engineered anti-PD-L1 antibody
  • TECENTRIQ
  • RO5541267
Drug: Cobimetinib
Oral repeating dose
Other Names:
  • GDC-0973
  • XL518
  • Cotellic
  • RO5514041
Drug: Vemurafenib
Oral repeating dose, depending on arm/cohort
Other Names:
  • Zelboraf
  • RO5185426
Experimental: ECC: Ate+Vem+Cob (No Mandatory Biopsy)
Expansion Cohort C (ECC): 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
Atezolizumab will be administered q3w or q2w.
Other Names:
  • MPDL3280A, an engineered anti-PD-L1 antibody
  • TECENTRIQ
  • RO5541267
Drug: Cobimetinib
Oral repeating dose
Other Names:
  • GDC-0973
  • XL518
  • Cotellic
  • RO5514041
Drug: Vemurafenib
Oral repeating dose, depending on arm/cohort
Other Names:
  • Zelboraf
  • RO5185426

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


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

Inclusion Criteria:

  • Histologic or cytologic documentation of metastatic or Stage IIIc unresectable melanoma, with BRAFV600 mutation as assessed by BRAFV600 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 performance status of 0 or 1
  • Adequate hematologic and end organ function
  • Measurable disease per RECIST v1.1
  • For women of childbearing potential, agreement to remain abstinent (refrain from heterosexual intercourse) or use two effective forms of contraceptive methods including at least one 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 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 A & B and optional, but encouraged in Escalation Cohorts 2 & 3 and Expansion Cohort C)

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 or PD-L1 targeted therapy or cytotoxic T-lymphocyte-associated antigen 4 targeted therapy including ipilimumab (this exclusion criterion does not apply to participants enrolled in Expansion Cohort A)
  • Receipt of prior mitogen-activated protein kinase inhibitor pathway agents including mitogen-activated protein 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 [CYP] 3A4 enzyme inducer) or grapefruit juice (potent CYP3A4 enzyme inhibitor) within 7 days preceding the start of study treatment to the end of 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
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01656642


Locations
United States, California
UCLA
Los Angeles, California, United States, 90024
The Angeles Clinic and Research Institute - W LA Office
Los Angeles, California, United States, 90025
United States, Colorado
University of Colorado Health Science Center; Biomedical Research Bldg. Room 511
Aurora, Colorado, United States, 80045
United States, Florida
Florida Cancer Specialists - Sarasota
Sarasota, Florida, United States, 34232
Florida Cancer Specialists
West Palm Beach, Florida, United States, 33401
United States, Massachusetts
Massachusetts General Hospital.
Boston, Massachusetts, United States, 02114
Beth Israel Deaconess Med Ctr
Boston, Massachusetts, United States, 02215
Dana Farber Can Ins
Boston, Massachusetts, United States, 02215
United States, Tennessee
Sarah Cannon Research Institute
Nashville, Tennessee, United States, 37203
United States, Texas
MD Anderson Cancer Center
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 ( EudraCT Number )
First Submitted: August 1, 2012
First Posted: August 3, 2012
Last Update Posted: August 16, 2017
Last Verified: August 2017

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


To Top