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Nilotinib in KIT-driven advanced melanoma: Results from the phase II single-arm NICAM trial
James Larkin1, Richard Marais2, Nuria Porta3
1Skin and Renal Units, The Royal Marsden Hospital NHS Foundation Trust, London, UK; Melanoma and Kidney Cancer Team, The Institute of Cancer Research, London, UK.
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).
Insights
Nilotinib shows activity in rare mucosal and acral melanomas with KIT mutations. This targeted therapy offers a new treatment option for patients with these difficult-to-treat melanoma subtypes.
Area of Science:
- Oncology
- Dermatology
- Pharmacology
Background:
- Mucosal melanoma (MM) and acral melanoma (AM) are rare subtypes with poor prognoses.
- KIT mutations are present in 15-20% of MM and AM, representing a potential therapeutic target.
- Currently, no small-molecule inhibitors targeting KIT mutations are approved for melanoma treatment.
Purpose of the Study:
- To investigate the safety and activity of nilotinib in patients with metastatic KIT-mutant mucosal melanoma and acral melanoma.
- To evaluate the efficacy of nilotinib in a rare subset of melanoma patients with unmet clinical needs.
Main Methods:
- A multicenter, single-arm, Phase II clinical trial (NICAM) was conducted.
- Patients with metastatic MM and AM harboring KIT mutations were treated with nilotinib.
- KIT mutations were identified using a ddPCR assay in circulating tumor DNA (ctDNA).
Main Results:
- Of 219 screened patients, 18% (39) had identified KIT mutations.
- Among 26 evaluable patients, 6 (25%) were progression-free at 6 months, and 5 (19%) achieved an objective response at 12 weeks.
- The median overall survival (OS) was 7.7 months, and the ddPCR assay detected KIT alterations in ctDNA in 16/17 patients.
Conclusions:
- Nilotinib demonstrates activity in KIT-mutant acral and mucosal melanomas, including non-hotspot mutations.
- These findings support the evaluation of nilotinib as a treatment option for KIT-mutated melanoma.
- Further clinical investigations of nilotinib for KIT-mutated melanoma are warranted.
