A Study of Vemurafenib and GDC-0973 (Cobimetinib) in Participants With BRAFV600E Mutation-Positive Metastatic Melanoma
Condition: Malignant Melanoma
MeSH terms: Melanoma
Intervention: Cobimetinib; vemurafenib
Intervention description: Participants will receive cobimetinib 60 to 100 mg at any of the 3 dosing schedules with or without vemurafenib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.; Participants will receive vemurafenib 720 or 960 mg along with cobimetinib in cycles of 28 days each until disease progression, unacceptable toxicity, or any other discontinuation criteria are met.
Intervention MeSH terms: Vemurafenib
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 131.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This open-label, dose-escalation study of vemurafenib in combination with cobimetinib will
      evaluate the safety, tolerability and pharmacokinetics in participants with BRAFV600
      mutation-positive metastatic melanoma. Participants with previously untreated, BRAFV600E
      mutation-positive, locally advanced/unresectable or metastatic melanoma or those who have
      progressed on vemurafenib monotherapy immediately prior to enrolling in this trial are
      eligible. Participants will be assigned to different cohorts with escalating oral doses of
      vemurafenib and cobimetinib. This study consists of 2 stages, Stage 1 (Dose Escalation Stage
      [DES] and Cohort Expansion Stage [CES]) and the anticipated time on study treatment is until
      disease progression, unacceptable toxicity or any other discontinuation criterion is met.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Participants with histologically confirmed melanoma (unresectable Stage IIIc and Stage
             IV metastatic melanoma, as defined by American Joint Committee on Cancer [AJCC])

          -  Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) Version
             (V) 1.1

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of less than or equal to
             (</=) 1

          -  Participants must

               1. be previously untreated for locally advanced/unresectable or metastatic melanoma
                  or

               2. previously treated but without prior exposure to any BRAF or MEK inhibitor
                  therapy or

               3. progressed on vemurafenib while participating in a Phase I (including clinical
                  pharmacology studies), II, or III clinical study or expanded access programs
                  (EAP) immediately prior to enrollment in this study or

               4. progressed on vemurafenib administered in a postmarketing setting immediately
                  prior to enrollment in this study.

          -  Life expectancy >/=12 weeks

        Exclusion Criteria:

          -  History of prior significant toxicity from another RAF or MEK pathway inhibitor
             requiring discontinuation of treatment

          -  Palliative radiotherapy within 2 weeks prior to first dose of study drug treatment

          -  Experimental therapy within 4 weeks prior to first dose of study drug treatment except
             vemurafenib

          -  Major surgery within 4 weeks of first dose of study drug treatment or planning a major
             surgery during the study