Patient case: 57-year-old male with melanoma; genetic feature: BRAF (V600E), PTEN loss of function

Clinical trial: A Phase III Study Comparing Vemurafenib vs Vemurafenib Plus Cobimetinib (GDC-0973) in Patients With Metastatic Melanoma

Summary: To evaluate the efficacy of vemurafenib in combination with cobimetinib (GDC-0973), compared with vemurafenib and placebo, in previously untreated BRAF V600 mutation-positive patients with unresectable locally advanced or metastatic melanoma, as measured by progression-free survival (PFS), assessed by the study site investigator.


Eligibility: Inclusion Criteria:
  -  Patients with histologically confirmed melanoma, either unresectable stage IIIc or stage IV metastatic melanoma, as defined by the American Joint Committee on Cancer 7th edition.
  -  Unresectability of stage IIIc disease must have confirmation from a surgical oncologist.
  -  Patients must be naïve to treatment for locally advanced unresectable or metastatic disease (ie, no prior systemic anti-cancer therapy for advanced disease; stage IIIc and IV). Prior adjuvant immunotherapy (including ipilimumab) is allowed.
  -  Documentation of BRAF V600 mutation-positive status in melanoma tumor tissue (archival or newly obtained tumor samples) using the cobas 4800 BRAF V600 mutation test.
  -  Measurable disease per Response Evaluation Criteria in Solid Tumors (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.
  Exclusion Criteria:
  -  History of prior rapidly accelerated fibrosarcoma (RAF) or mitogen-activated protein kinase (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 treatment.
  -  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 ophthalmological examination that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion (RVO), or neovascular macular degeneration.
  -  Uncontrolled glaucoma with intraocular pressure.
  -  Serum cholesterol ≥ Grade 2.
  -  Hypertriglyceridemia ≥ Grade 2.
  -  Hyperglycemia (fasting) ≥ Grade 2.
  -  History of clinically significant cardiac dysfunction.
  -  Patients with active central nervous system (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, AND
  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 study drugs.
  -  Pregnant, lactating, or breast feeding women.

Relevance to patient case: definitely relevant