Larkin, James, Marais, Richard, Porta, Nuria, Gonzalez de Castro, David, Parsons, Lisa, Messiou, Christina, Stamp, Gordon, Thompson, Lisa, Edmonds, Kim, Sarker, Sarah et al (show 13 more authors)
(2024)
Nilotinib in KIT-driven advanced melanoma: Results from the phase II single-arm NICAM trial.
Cell reports. Medicine, 5 (3).
101435-.
Abstract
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).
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Humans, Melanoma, Skin Neoplasms, Pyrimidines, Antineoplastic Agents, Proto-Oncogene Proteins c-kit |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Systems, Molecular and Integrative Biology |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 23 Apr 2024 08:49 |
| Last Modified: | 23 Apr 2024 08:49 |
| DOI: | 10.1016/j.xcrm.2024.101435 |
| Open Access URL: | https://doi.org/10.1016/j.xcrm.2024.101435 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3180525 |
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