SU2C GEMM Trial

The goal of the GEMM Trial is to ascertain if comprehensive and systematic interrogation of a patient's tumor molecular profile improves outcomes compared to the current practice of physician's choice for metastatic melanoma patients who have progressed following first line therapy. The data shared here includes tumor/normal exome and tumor RNAseq data for the trial patients, as well as archival data for a subset of patients.]]> Inclusion criteria: Patients aged ≥18 years with metastatic or locally advanced and unresectable BRAFwt melanoma who had either progressed following previous treatment with ipilimumab and/or interleukin-2, or were not eligible for treatment with interleukin-2 or ipilimumab, and were eligible to participate in this study. Other criteria included life expectancy ≥3 months; tumor accessible by interventional radiology or surgical intervention; measurable disease as defined by RECIST v1.1 criteria; Eastern Cooperative Oncology Group performance status of ≤2; ability to tolerate oral medication; and adequate organ and marrow function defined by: Hemoglobin ≥ 9 g/dL, Leukocytes ≥ 3,000/microliter (mcL), Absolute neutrophil count (ANC) ≥1,500/mcL, Platelets (PLT) ≥100,000/mcL, Aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN) or ≤ 5 x ULN if liver metastases were present, Alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN) or ≤ 5 x ULN if liver metastases were present, Alkaline phosphatase ≤ 2.0 x ULN or ≤ 5 x ULN if bone or liver metastases were present, Bilirubin ≤ 1.5 x ULN, and Creatine ≤ 1.5 x ULN or creatine clearance ≥ 50 mL/min. Exclusion criteria: Patients were excluded if they had prior cytotoxic chemotherapy treatment of metastatic melanoma; active infection at time of surgery; peripheral neuropathy ≥ Grade 2; evidence of severe or uncontrolled systemic disease(s) including known cases of Hepatitis B or C or human immunodeficiency virus (HIV); active progressive brain metastases; treatment with other anti-cancer therapy (cytotoxic, biologic, radiation, or hormonal other than for replacement) except for medications that were prescribed for supportive care but may potentially had an anti-cancer effect if started ≥ 1 month prior to enrollment; prior history of seizures within the past year unrelated to brain metastases; pre-existing cardiac conditions; LVEF <45%; stroke or myocardial infarction within 6 months before the first dose of treatment; acute gastrointestinal bleeding within 1 month of study entry; QTcF ≥450 msec for males and QTcF ≥470 for females at time of screening; malabsorption syndrome or other condition that would interfere with intestinal absorption or ability to swallow oral medication; pregnant or nursing women; previous organ transplant; major surgery within 14 days of enrollment; diagnosis or treatment for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, or an in situ malignancy; and patients requiring chronic maintenance of red blood cell, white blood cell or granulocyte counts through the use of blood transfusions or growth factor support.]]>