A PHASE III, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF VEMURAFENIB VERSUS VEMURAFENIB PLUS GDC-0973 IN PREVIOUSLY UNTREATED BRAFV600-MUTATION POSITIVE PATIENTS WITH UNRESECTABLE LOCALLY ADVANCED OR METASTATIC MELANOMA
- Patients with histologically confirmed melanoma, either unresectable stage IIIc or
stage IV metastatic melanoma, as defined by the American Joint Committee on Cancer
- Unresectability of stage IIIc disease must have confirmation from a surgical
- Patients must be naïve to treatment for locally advanced unresectable or metastatic
disease (i.e., no prior systemic anti-cancer therapy for advanced disease; stage IIIc
and IV). Prior adjuvant immunotherapy (including ipilimumab) is allowed.
- Documentation of BRAFV600 mutation-positive status in melanoma tumor tissue (archival
or newly obtained tumor samples) using the cobas 4800 BRAF V600 mutation test.
- Measurable disease per RECIST v1.1.
- Eastern Clinical Oncology Group performance status of 0 or 1.
- Consent to provide archival for biomarker analyses.
- Consent to undergo tumor biopsies for biomarker analyses.
- Life expectancy >/= 12 weeks.
- Adequate hematologic and end organ function
- History of prior RAF or MEK pathway inhibitor treatment.
- Palliative radiotherapy within 14 days prior to the first dose of study treatment.
- Major surgery or traumatic injury within 14 days prior to first dose of study
- Active malignancy other than melanoma that could potentially interfere with the
interpretation of efficacy measures. Patients with a previous malignancy within the
past 3 years are excluded except for patients with resected basal cell carcinoma
(BCC) or squamous cell carcinoma (SCC) of the skin, melanoma in-situ, carcinoma
in-situ of the cervix, and carcinoma in-situ of the breast.
- History of or evidence of retinal pathology on ophthalmologic examination that is
considered a risk factor for neurosensory retinal detachment, retinal vein occlusion
(RVO), or neovascular macular degeneration.
- Uncontrolled glaucoma with intra-ocular pressures
- Serum cholesterol >/= Grade 2
- Hypertriglyceridemia >/= Grade 2
- Hyperglycemia (fasting) >/= Grade 2
- History of clinically significant cardiac dysfunction
- Patients with active CNS lesions (including carcinomatous meningitis) are excluded.
However, patients are eligible if:
1. All known CNS lesions have been treated with stereotactic therapy or surgery,
2. There has been no evidence of clinical and radiographic disease progression in
the CNS for >/= 3 weeks after radiotherapy or surgery
- Current severe, uncontrolled systemic disease.
- History of malabsorption or other condition that would interfere with absorption of
- Pregnant, lactating, or breast feeding.