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

This study is currently recruiting participants.
Verified April 2014 by Genentech
Sponsor:
Information provided by (Responsible Party):
Genentech
ClinicalTrials.gov Identifier:
NCT01656642
First received: August 1, 2012
Last updated: April 7, 2014
Last verified: April 2014
  Purpose

This is an open-label, multicenter, Phase Ib, dose-escalation and cohort-expansion study of MPDL3280A in combination with Vemurafenib (Zelboraf®) in previously untreated patients with BRAFV600-mutation positive metastatic melanoma.


Condition Intervention Phase
Malignant Melanoma
Drug: MPDL3280A
Drug: Vemurafenib (Zelboraf®)
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 (Zelboraf®) in Patients With Previously Untreated BRAFV600-Mutation Positive Metastatic Melanoma

Resource links provided by NLM:


Further study details as provided by Genentech:

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: December 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A
MPDL3280A + Zelboraf (vemurafenib)
Drug: MPDL3280A
Intravenous repeating dose
Drug: Vemurafenib (Zelboraf®)
Oral repeating dose
Experimental: B
MPDL3280A + Zelboraf (vemurafenib)
Drug: MPDL3280A
Intravenous repeating dose
Drug: Vemurafenib (Zelboraf®)
Oral repeating dose
Experimental: C
MPDL3280A + Zelboraf (vemurafenib)
Drug: MPDL3280A
Intravenous repeating dose
Drug: Vemurafenib (Zelboraf®)
Oral repeating dose

  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 an effective form of contraception and to continue its use for 6 months after discontinuation from the study

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 </= 14 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
  • Known primary central nervous system (CNS) malignancy or untreated or active CNS metastases
  • Any ongoing malignancy other than 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 Cycle 1 Day 1 or Signs or symptoms of infection within 2 weeks prior to Cycle 1 Day 1
  • Received oral or IV antibiotics within 2 weeks prior to Cycle 1 Day 1
  • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1 or anticipation that such a live attenuated vaccine will be required during the study
  • History of clinically significant cardiac or pulmonary dysfunction
  • Treatment with systemic immunosuppressive medications within 4 weeks prior to Cycle 1 Day 1
  • Bisphosphonate therapy for symptomatic hypercalcemia
  • Pregnant or lactating women
  • Any vemurafenib-specific exclusion criteria
  Contacts and Locations
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
Investigators
Study Director: Clinical Trials Genentech
  More Information

No publications provided

Responsible Party: Genentech
ClinicalTrials.gov Identifier: NCT01656642     History of Changes
Other Study ID Numbers: GP28384
Study First Received: August 1, 2012
Last Updated: April 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Genentech:
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

ClinicalTrials.gov processed this record on April 23, 2014