815P A single-arm, phase II clinical study of imatinib mesylate/toripalimab combo in patients (pts) with advanced melanoma harboring c-Kit mutation or amplification

Kit inhibitor monotherapy has moderated activity in melanoma harboring c-Kit aberrations (CKA) but with an unsatisfied objective response rate (ORR) of 23-26% and median progression free survival (mPFS) of 3.5-7.3mo. Thus we performed a phase II trial testing the imatinib mesylate/toripalimab (anti-PD-1 monoantibody) combo in pts with advanced melanoma harboring CKA. (NCT: 05274438). This is a single-arm, single-center, phase II clinical trial involving 37 pts (treatment-naive or refractory to standard therapy excluding Kit inhibitors and anti-PD-1/L1) with advanced melanoma harboring CKA including two stages: 3 pts were enrolled starting with imatinib 400mg qd for 6 weeks, followed by imatinib 400mg qd combined with toripalimab 240mg per 3 weeks until disease progression or intolerable toxicity. If dose limiting toxicity (DLT) was not observed, the original dose was extended to 37 pts in stage II; if there was 1 DLT, pts was extended to 6 in stage I; if ≥2 DLT cases occurred, imatinib was reduced to 300mg qd and the "3+3" study was restarted. The primary endpoint was PFS and the secondary endpoints included ORR, disease control rate (DCR), overall survival (OS) and safety. From March 2021 to April 2022, no DLT was observed in the first 3 pts and another 17 pts enrolled. 17 pts were radiologically evaluable. The ORR was 58.8% (95% CI: 32.7-84.9%) and DCR was 82.4% (95% CI: 56.6-96.2%). The mPFS was not reached (NR). Notably, in pts harboring exon 11 mutations (n=10), the ORR was 90.0% (95% CI: 55.5-99.7%). In 9 treatment naive pts, the ORR was 55.6% (95% CI: 21.2-86.3). The incidence of grade ≥3 treatment-related adverse events was 20% (4/20), including rash (10.0%), aspartase transaminase elevation (5.0%), fatigue (5.0%) and interstitial pneumonia (5.0%). No treatment-related deaths was observed. Imatinib mesylate/toripalimab combo was effective and well-tolerated in pts with advanced melanoma harboring c-kit aberrations. Longer follow-up and further patient recruitment are in need.