A Phase 3 Study to Compare Efficacy and Safety of Masitinib to Dacarbazine in the Treatment of Patients With Non-Resectable or Metastatic Stage 3 or Stage 4 Melanoma Carrying a Mutation in the Juxta Membrane Domain of C-Kit

Masitinib is a novel TKI that potently inhibits wild type (WT) c-kit and its activated form, mutated in the juxtamembrane region (JM c-kit) PDGFRs, the intracellular kinase Lyn, and to a lesser extent fibroblast growth factor receptor 3 (FGFR3).

Pre-clinical data suggest that masitinib is a strong candidate for the treatment of patients with advanced melanoma carrying a c-kit JM mutation.

• Drug: masitinib
  masitinib 7.5 mg/kg/day
• Drug: Dacarbazine
  dacarbazine IV bolus at 1,000 mg/m2 once every three weeks

• Experimental: masitinib
  Intervention: Drug: masitinib
• Active Comparator: dacarbazine
  Intervention: Drug: Dacarbazine

Inclusion Criteria:

• Patient with histologically or cytologically confirmed non-resectable or metastatic stage 3 (non-resectable IIIB or IIIC, AJCC TNM staging system 7th edition) or stage 4 melanoma
• Patient with detectable c-kit JM mutation confirmed by DNA or RNA sequencing, which is expected to be mainly found after screening of mucosal or acral melanoma or melanoma on skin with chronic sun-induced damages (defined by a microscopically marked elastosis involving the skin surrounding their primary melanoma)
• Patient with measurable disease according to RECIST
• Patient with ECOG ≤ 2

Exclusion Criteria:

• Patient with other malignancies from which the patient has been continuously disease-free for < 3 years, with the exception of melanoma, cervical carcinoma in situ, basal cell or squamous cell skin cancer, ductal or lobular carcinoma in situ of the breast

• Patient with active brain metastases are not eligible. Patients with treated brain metastases are eligible if :

  • presence of 3 brain lesions or less
  • lesion(s) diameter is ≤ 2 cm
  • radiation therapy (gamma knife) was completed ≥ 4 weeks prior to baseline
  • surgery was completed ≥4 weeks prior to baseline
  • lesions assessed by follow-up scan (or MRI if MRI performed before brain therapy) ≥ 1 month after brain therapy are considered under control at baseline
• Patient refractory to dacarbazine defined as patient presenting a disease progression after 3 months of dacarbazine therapy.
• Prior treatment with a tyrosine kinase c-kit inhibitor