Regorafenib in Caucasian patients with pretreated advanced KIT-mutant melanoma: A dual center case series

BackgroundOncogenic KIT-mutations (KIT mut) are found in +/- 3% of melanoma patients (pts), most frequently in mucosal (15-21%), acro-lentiginous (11-23%), and melanoma arising on sun-damaged skin (CSDS; 16-27%). Only a minority of pts (20-30%) responds to treatment with small molecule KIT-inhibitors (e.g, imatinib, sunitinib, nilotinib, dasatinib). The activity of regorafenib (REGO, a multi-targeted small molecule inhibitor of KIT, TIE2, VEGFR, PDGFR, RET, RAF, and CSF-1R kinases) has never been studied in a Caucasian population with KIT-mutant melanoma.MethodsThe outcome of a prospectively identified cohort of advanced KIT mut melanoma pts treated with REGO at two medical centers in the EU was investigated (database lock (DBL): 25APR2024).ResultsEight patients were included: median age 60.7 years [range 41-76]; Caucasian (100%); AJCC stage IV-M1c: 7 pts, and -M1d: 1 pt; elevated baseline LDH: 3 pts; ECOG performance status 0 and 1: resp. 6- and 2 pts); primary mucosal 2-, acro-lentiginous 3-, and CSDS 3 pts. Oncogenic KIT mut were documented in exon 11 (n=5), -13 (n=2), and -17 (n=1). Three pts participated in the prospective REGOMEL phase II clinical trial and 4 pts were treated on a compassionate use basis. All pts were pretreated and had previously progressed on anti-PD-1 and -CTLA-4 based therapy, 3 pts on imatinib. REGO was administered orally, once daily (QD), continuously, at a dose of 40 to 120 mg (n=7), or on a 21/28d regimen of 120 mg QD (n=1). In 7 response evaluable pts, the best overall responses (RECIST v. 1.1) were 1 complete response and 6 partial responses (overall response rate 100%, all responses were confirmed). After a median follow-up of 43w [range 3-65w], treatment and responses were ongoing in respectively 6 and 4 pts. Median duration of response was not reached [range 6-59w]. Median progression free survival was not reached and all pts were alive at DBL. All pts had at least 1 TRAE. Grade 3 TRAE included arterial hypertension, and digestive bleeding (n=1, each).ConclusionsREGO demonstrated a manageable safety profile and high anti-tumor activity in this Caucasian population of pretreated advanced KIT mut melanoma pts deserving further evaluation in a prospective clinical trial.Legal entity responsible for the studyThe authors.FundingBayer.DisclosureI. Dirven: Financial Interests, Institutional, Research Funding: Kom op tegen kanker; Financial Interests, Personal, Other, travel, accommodation, expenses: AstraZeneca, Pierre Fabre; Non-Financial Interests, Institutional, Research Funding: Bayer. M. Vounckx: Financial Interests, Institutional, Research Funding: Kom op tegen kanker. J.I. Kessels: Financial Interests, Personal, Invited Speaker: BMS, Janssen; Financial Interests, Institutional, Research Funding: Kom op tegen kanker; Financial Interests, Personal, Other, Expenses/education: Safoni/Regeneron, Janssen. M. Mandalà: Financial Interests, Personal, Advisory Board: MSD, Novartis, Sanofi, BMS, Pierre Fabre; Financial Interests, Personal, Invited Speaker: SunPharma. B. Neyns: Financial Interests, Institutional, Advisory Board: Novartis, Bristol Myers Squibb, Pierre Fabre, MSD (Merck Sharp & Dohme); Financial Interests, Institutional, Research Grant: Novartis, Pfizer; Non-Financial Interests, Institutional, Product Samples: Bayer. All other authors have declared no conflicts of interest.