Nilotinib in KIT-driven advanced melanoma: Results from the phase II single-arm NICAM trial.
Date
2024-03-19Author
Larkin, J
Marais, R
Porta, N
Gonzalez de Castro, D
Parsons, L
Messiou, C
Stamp, G
Thompson, L
Edmonds, K
Sarker, S
Banerji, J
Lorigan, P
Evans, TRJ
Corrie, P
Marshall, E
Middleton, MR
Nathan, P
Nicholson, S
Ottensmeier, C
Plummer, R
Bliss, J
Valpione, S
Turajlic, S
Type
Journal Article
Metadata
Show full item recordAbstract
Mucosal (MM) and acral melanomas (AM) are rare melanoma subtypes of unmet clinical need; 15%-20% harbor KIT mutations potentially targeted by small-molecule inhibitors, but none yet approved in melanoma. This multicenter, single-arm Phase II trial (NICAM) investigates nilotinib safety and activity in KIT mutated metastatic MM and AM. KIT mutations are identified in 39/219 screened patients (18%); of 29/39 treated, 26 are evaluable for primary analysis. Six patients were alive and progression free at 6 months (local radiology review, 25%); 5/26 (19%) had objective response at 12 weeks; median OS was 7.7 months; ddPCR assay correctly identifies KIT alterations in circulating tumor DNA (ctDNA) in 16/17 patients. Nilotinib is active in KIT-mutant AM and MM, comparable to other KIT inhibitors, with demonstrable activity in nonhotspot KIT mutations, supporting broadening of KIT evaluation in AM and MM. Our results endorse further investigations of nilotinib for the treatment of KIT-mutated melanoma. This clinical trial was registered with ISRCTN (ISRCTN39058880) and EudraCT (2009-012945-49).
Collections
Subject
KIT mutation
acral
liquid biopsy
melanoma
mucosal
tyrosine kinase inhibitor
Humans
Melanoma
Antineoplastic Agents
Proto-Oncogene Proteins c-kit
Skin Neoplasms
Pyrimidines
Research team
Clin Trials & Stats Unit
Language
eng
Date accepted
2024-01-26
License start date
2024-03-19
Citation
Cell Reports Medicine, 2024, 5 (3), pp. 101435 -
Publisher
Elsevier BV