Phase Ii Multicentric Uncontrolled National Trial Assessing the Efficacy of Nilotinib in the Treatment of Advanced Melanomas with C-Kit Mutation or Amplification.

9032 Background: Three phase II trials have shown an overall response rate (ORR) around 20% with imatinib in melanoma carrying KIT mutations. The aim of this study was to study the interest of nilotinib a Kit inhibitor with pharmacological advantages compared to imatinib. Methods: this multicenter uncontrolled open Hern’s single-stage Phase II study enrolled patients with advanced melanoma and KIT amplifications and/or mutations and no BRAF and NRAS mutation, nor previous Kit targeted therapy or active brain metastasis.Patients received Nilotinib 400 mg bid. ORR was the primary endpoint. Secondary endpoints included disease control, metabolic response rate and biomarkers associated to response . Based on type I and II error rates fixed at 0.05 and 0.10, respectively, a sample size of 25 patients was required to test the level of response, p≤ 7.5% against > 30%, with at least 5 successes tindicating that the treatment was effective. Analysis was based on intent to treat. Results: 25 patients were enrolled from 2010-07-27 to 2012-08-27: 13 females (52%); median age 70 years(range, 43-87); 23 (92%) tumors with KIT mutations, 5 (20%) KIT amplifications, and 3 (12%) both. One patient (4%) had primary unresectable melanoma, 3(12%) unresectable stage III melanoma, 21 (84%) stage IV melanoma .13 (52%) patients were chemotherapy naive, 12 (48%) had previously received dacarbazine or fotemustine, 1 immunotherapy . Median follow-up was 3 months ([IQR: 2-7], range 0.3-12).One patient reached CR and 4 partial responses, concluding to treatment effectiveness with an ORR of 20% (95%CI: 6.8-40.7) all in patients with KIT mutation . Six patients died and 1-year overall survival was 68.3% (95%CI: 46.5-1.00).The 25 patients experienced a total of 236 adverse events , 2/3 imputed to the drug mostly of grade 1 (n=146 in 21 patients) and grade 2 (47 in 13 pts), and less frequently of grade 3 (39 in 18 pts) or grade 4 (3 in 3 pts: 2 dyspnea, 1 renal failure) and 1 death. Five patients had drug withdrawal because of toxicity. Conclusions: According to our hypothesis, nilotinib is an effective drug in KIT mutated melanoma in the absence of BRAF and NRAS mutations and should be added to our armamentarium. Clinical trial information: NCT01168050.