1112P - Phase II study of nilotinib in melanoma harboring KIT alterations following progression or intolerance to prior KIT inhibition

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anticancer Agents
Skin Cancers
Translational Research
Basic Principles in the Management and Treatment (of cancer)
Biological Therapy
Presenter Richard Carvajal
Citation Annals of Oncology (2014) 25 (suppl_4): iv374-iv393. 10.1093/annonc/mdu344
Authors R. Carvajal1, D. Lawrence2, J.S. Weber3, T.F. Gajewski4, R. Gonzalez5, J. Lutzky6, S. O'Day7, O. Hamid8, J.D. Wolchok9, P. Chapman9, R.J. Sullivan10, J.B. Teitcher11, C. Antonescu12, M.C. Heinrich13, B. Bastian14, C.L. Corless15, A. Giobbie-Hurder16, J. Fletcher17, F.S. Hodi18
  • 1Medicine, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 2Medicine, Massachusetts General Hospital Cancer Center, Boston/US
  • 3Medicine, H. Lee Moffitt Cancer Center University of South Florida, 33612 - Tampa/US
  • 4Department Of Pathology And Department Of Medicine, University of Chicago, Chicago/US
  • 5Medicine/ Medical Oncology, University of Colorado Cancer Center Anschutz Cancer Pavilion, 80045 - Aurora/US
  • 6Medical Oncology, Mount Sinai Comprehensive Cancer Center, Miami Beach/US
  • 7Usc Keck School Of Medicine, The Los Angeles Skin Cancer Institute, The Beverly Hills Cancer Center, Santa Monica/US
  • 8Melanoma Center, The Angeles Clinic and Research Institute, Los Angeles/US
  • 9Melanoma And Immunotherapeutics Service, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 10Medicine, Massachusetts General Hospital Cancer Center, 02114 - Boston/US
  • 11Radiology, Memorial Sloan Kettering Cancer Center, New York/US
  • 12Pathology, Memorial Sloan-Kettering Cancer Center, New York/US
  • 13Portland Va Medical Center, Oregon Helath & Science University and OHSU Knight Cancer Institute, 97239 - Oregon/US
  • 14Pathology, Helen Diller Family Comprehensive Cancer Center, San Francisco/US
  • 15Pathology, 10Oregon Health & Science University, Portland/US
  • 16Biostatistics And Computational Biology, Dana-Farber Cancer Institute, Boston/US
  • 17Pathology, Brigham and Women's Hospital, Boston/US
  • 18Melanoma Center, Dana-Farber Cancer Institute, Boston/US



Durable responses can be achieved with KIT inhibitors (KI) such as imatinib in melanomas harboring KIT alterations. The efficacy of second-line KIs after progression on other therapies and the activity of KIs against brain metastases are unknown.


We conducted a phase II study of nilotinib 400 mg PO BID in patients(pts) with melanomas harboring KIT mut or amplification(amp) who were either refractory or intolerant to prior KITi (Cohort A)or who had brain metastases regardless of prior therapy (Cohort B). The primary endpoint was 4-month(mo) disease control rate(DCR). Secondary endpoints included response rate, time-to-progression(TTP) and overall survival(OS). Response was measured every eight weeks(wks) for 32 wks and every 12 wks subsequently using RECIST 1.0. Brain imaging was included for those with CNS involvement. A Simon 2-stage and a single-stage design was planned to assess for the primary endpoint in Cohorts A and B, respectively. If ≥3 of 25 pts and ≥2 of 10 pts in Cohorts A and B, respectively, achieved disease control at 4 mos, then nilotinib would be considered promising in these settings.


20 pts were enrolled and 19 treated (11-Cohort A; 8-Cohort B): 14 female; median age 67 years (range 38-85); 16-prior imatinib, 1-prior imatinib and sorafenib, 3-prior ipilimumab; 12-KITmut alone, 2-KITamp alone, 6-both KITmut and amp. 3 pts on Cohort A (27%; 95% CI, 8% - 56%) and 1 pt on Cohort B (12.5%; 90% CI, 0.6% - 47%) achieved the primary endpoint of disease control at 4 mos. 2 partial responses were observed in Cohort A (18.2%, 90% CI, 3% - 47%); none were observed in Cohort B. Median TTP and OS was 3.3 (90% CI, 2.1–3.9 mos) and 9.1 mos (90% CI, 4.3–14.2 mos), respectively, in all treated pts. Radiographic responses were observed within the brain in 2 pts on Cohort B; however, the median TTP and OS in Cohort B was 2.6 (90% CI, 1.8–3.9) and 4.3 mos (90% CI, 3.5–11.9), respectively. Enrollment was closed prior to completing either Cohorts A or B due to accrual challenges.


Nilotinib can achieve disease control in pts with melanoma harboring KIT alterations after progression on a prior tyrosine kinase inhibitor. Efficacy of this agent against brain metastasis is limited.


R. Carvajal: Consultant - Novartis, AstraZeneca Scientific Advisory Board - Aura Biosciences; J.S. Weber: Honoraria - Novartis Advisory Board - Novartis Research Funding to Institution–Novartis; T.F. Gajewski: Consultant - Roche/Genentech, Bayer, B-I, AbbVie, Jounce Research Funding - BMS, Incyte, Roche/Genentech, Merck, GSK-BIO; R. Gonzalez: Honoraria - Roche/Genentech Consulting - Roche/Genentech, GSK, Piramal Research Funding - Roche/Genentech, GSK, Piramal, Millenium, Novartis J. Lutzky: Grants - Novartis Research Funding - Medimmune, Bayer, Prometheus, Merck, BMS, Viralytics, Incyte, Genentech/Roche, GSK, Merck-Serono Personal Fees: BMS, Genentech; S. O'Day: Research Funding–Novartis; J.D. Wolchok: Consulting - BMS, Merck, Medimmune Research Funding - BMS, Merck, Medimmune, Novartis; M.C. Heinrich: Research Grant - Novartis Consulting Fees - Novartis, MolecularMD Clinical Studies - Novartis Equity Interest–MolecularMD; B. Bastian: Dr. Bastian reports personal fees from Novartis, outside the submitted work; In addition, Dr. Bastian has a patent detection of c-kit mutations in melanoma pending; C.L. Corless: Dr. Corless reports grants and personal fees from Novartis, outside the submitted work; F.S. Hodi: Dr. Hodi reports personal fees from Novartis, outside the submitted work. other authors have declared no conflicts of interest.