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A Phase 1b Study of MPDL3280A (an Engineered Anti-PDL1 Antibody) in Combination With Vemurafenib (Zelboraf®) or Vemurafenib Plus Cobimetinib in Patients With Previously Untreated BRAFV600-Mutation Positive Metastatic Melanoma

This study is currently recruiting participants. (see Contacts and Locations)
Verified November 2014 by Genentech, Inc.
Sponsor:
Information provided by (Responsible Party):
Genentech, Inc.
ClinicalTrials.gov Identifier:
NCT01656642
First received: August 1, 2012
Last updated: November 4, 2014
Last verified: November 2014
  Purpose

This is an open-label, multicenter, Phase Ib, dose-escalation and cohort-expansi on study of MPDL3280A in combination with vemurafenib (Zelboraf®) or vemurafeni b plus cobimetinib in previously untreated patients with BRAFV600-mutation posit ive metastatic melanoma. Enrolled patients may continue treatment until they are no longer experiencing clinical benefit as assessed by the investigator.


Condition Intervention Phase
Malignant Melanoma
Drug: MPDL3280A
Drug: Vemurafenib (Zelboraf®)
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 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: 21 days following the first administration of MPDL3280A ] [ Designated as safety issue: No ]
  • Nature of dose-limiting toxicities (DLTs) [ Time Frame: 21 days following the first administration of MPDL3280A ] [ 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-MPDL3280A 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: 44
Study Start Date: August 2012
Estimated Study Completion Date: July 2017
Estimated Primary Completion Date: March 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
MPDL3280A + Zelboraf (vemurafenib)
Drug: MPDL3280A
Intravenous administration, fixed at either 15 or 20 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. Patients currently in Cohorts 2 and 3 still receiving MPDL3280A therapy (and any newly enrolled patients) will be switched to receive a fixed dose of 1200 mg q3w MPDL3280A formulation.
Drug: Vemurafenib (Zelboraf®)
Oral repeating dose, depending on arm/cohort
Experimental: 2
MPDL3280A + Zelboraf (vemurafenib)
Drug: MPDL3280A
Intravenous administration, fixed at either 15 or 20 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. Patients currently in Cohorts 2 and 3 still receiving MPDL3280A therapy (and any newly enrolled patients) will be switched to receive a fixed dose of 1200 mg q3w MPDL3280A formulation.
Drug: Vemurafenib (Zelboraf®)
Oral repeating dose, depending on arm/cohort
Experimental: 3
MPDL3280A + Zelboraf (vemurafenib)
Drug: MPDL3280A
Intravenous administration, fixed at either 15 or 20 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. Patients currently in Cohorts 2 and 3 still receiving MPDL3280A therapy (and any newly enrolled patients) will be switched to receive a fixed dose of 1200 mg q3w MPDL3280A formulation.
Drug: Vemurafenib (Zelboraf®)
Oral repeating dose, depending on arm/cohort
Experimental: 4
MPDL3280A + Zelboraf (vemurafenib) + cobimetinib
Drug: MPDL3280A
Intravenous administration, fixed at either 15 or 20 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. Patients currently in Cohorts 2 and 3 still receiving MPDL3280A therapy (and any newly enrolled patients) will be switched to receive a fixed dose of 1200 mg q3w MPDL3280A formulation.
Drug: Vemurafenib (Zelboraf®)
Oral repeating dose, depending on arm/cohort
Drug: cobimetinib
Oral repeating dose
Other Name: GDC-0973; XL518
Experimental: 5
MPDL3280A + Zelboraf (vemurafenib) + cobimetinib
Drug: MPDL3280A
Intravenous administration, fixed at either 15 or 20 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. Patients currently in Cohorts 2 and 3 still receiving MPDL3280A therapy (and any newly enrolled patients) will be switched to receive a fixed dose of 1200 mg q3w MPDL3280A formulation.
Drug: Vemurafenib (Zelboraf®)
Oral repeating dose, depending on arm/cohort
Drug: cobimetinib
Oral repeating dose
Other Name: GDC-0973; XL518
Experimental: Expansion
Up to 14 additional patients in two cohorts for each arm
Drug: MPDL3280A
Intravenous administration, fixed at either 15 or 20 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. Patients currently in Cohorts 2 and 3 still receiving MPDL3280A therapy (and any newly enrolled patients) will be switched to receive a fixed dose of 1200 mg q3w MPDL3280A formulation.
Drug: Vemurafenib (Zelboraf®)
Oral repeating dose, depending on arm/cohort
Drug: cobimetinib
Oral repeating dose
Other Name: GDC-0973; XL518

  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 melanoma, with BRAFV600 mutation as assessed by cobas® 4800 BRAF V600 Mutation Test. Origin of the primary tumor must be known and may be of skin, mucosal, or acral locations but not of ocular origin.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Adequate hematologic and end organ function
  • Measurable disease per RECIST v1.1
  • For female patients of childbearing potential and male patients with partners of childbearing potential, agreement to use two effective forms of contraception and to continue its use for 6 months after completion of study therapy

Exclusion Criteria:

  • Receipt of prior systemic anti-cancer therapy for unresectable, locally advanced or metastatic melanoma
  • Receipt of prior MAPK inhibitor pathway agents, including 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 </= 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 CT or MRI evaluation during screening and prior assessments for CNS metastases
  • Any active malignancy other than BRAF-mutated melanoma
  • History or risk of autoimmune disease
  • History of idiopathic pulmonary fibrosis, risk of pulmonary toxicity, or evidence of active pneumonitis on screening chest CT scan
  • History of HIV or hepatitis C infection
  • Active tuberculosis
  • Severe infections within 4 weeks prior to Study Day 1 or Signs or symptoms of infection within 2 weeks prior to Study Day 1
  • Received oral or IV antibiotics within 2 weeks prior to Study Day 1
  • Administration of a live, attenuated vaccine within 4 weeks before Study 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 patients to be enrolled into the vemurafenib+cobimetinib+MPDL3280A cohorts (D and E): 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 Study Day 1
  • Bisphosphonate therapy for symptomatic hypercalcemia
  • Pregnant or lactating women
  • Any vemurafenib-specific or cobimetinib-specific exclusion criteria
  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, 90025
United States, Florida
Recruiting
Sarasota, Florida, United States, 34232
United States, Massachusetts
Recruiting
Boston, Massachusetts, United States, 02215
Recruiting
Boston, Massachusetts, United States, 02114
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
Study First Received: August 1, 2012
Last Updated: November 4, 2014
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 November 25, 2014