Brief Summary

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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"

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.

• Study Type: Interventional
• Study Design: Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
• Study Primary Completion Date: January 2014

Interventions Used in this Clinical Trial

• Drug: MPDL3280A
  • Intravenous repeating dose
• Drug: Vemurafenib (Zelboraf®)
  • Oral repeating dose

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: A
  • MPDL3280A + Zelboraf (vemurafenib)
• Experimental: B
  • MPDL3280A + Zelboraf (vemurafenib)
• Experimental: C
  • MPDL3280A + Zelboraf (vemurafenib)

Outcome Measures for this Clinical Trial

Primary Measures

• Incidence of dose-limiting toxicities (DLTs)
  • Time Frame: 21 days following the first administration of MPDL3280A
    Safety Issue?: No
• Nature of dose-limiting toxicities (DLTs)
  • Time Frame: 21 days following the first administration of MPDL3280A
    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
    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
    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
    Safety Issue?: No

Secondary Measures

• Incidence of anti-MPDL3280A antibodies
  • Time Frame: approximately 12 months
    Safety Issue?: No
• Change in vital signs, including electrocardiograms (ECGs)
  • Time Frame: approximately 12 months
    Safety Issue?: No
• Change in clinical laboratory results
  • Time Frame: approximately 12 months
    Safety Issue?: No
• Number of cycles and dose intensity of each component of the treatment regimen
  • Time Frame: approximately 12 months
    Safety Issue?: No

Criteria for Participation in this Clinical Trial

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial: No

Clinical Trial Investigator Information

• Lead Sponsor
  • Genentech
• Provider of Information About this Clinical Study
  • Sponsor
• Overall Official(s)
  • Clinical Trials, Study Director, Genentech
• Overall Contact(s)
  • Please reference Study ID Number: GP28384 www.roche.com/about_roche/roche_worldwide.htm, 888-662-6728 (U.S. Only), genentechclinicaltrials@druginfo.com