Results from an ongoing phase 1 trial of a KIT-mutated or KIT-amplified melanoma cohort were presented at the virtual 2021 ESMO Congress to highlight the use of ripretinib, a kinase switch-control inhibitor designed to inhibit KIT mutations and effectively treat patients with advanced gastrointestinal stromal tumors (GIST) with prior exposure to tyrosine kinase inhibitors (TKIs).

“There are no approved TKIs for KIT-altered metastatic melanoma; ESMO and NCCN guidelines recommend specified KIT inhibitors as second-line therapy in certain situations,” explained Filip Janku, MD, PhD, Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, and co-investigators.

Further, reports of objective response rate (ORR) stands at typically <20% and progression-free survival (PFS) is limited to 3 to 4 months.

Patients with KIT-altered melanoma were assigned to the expansion arm and received treatment of ripretinib at the recommended phase 2 dose of 150 mg once daily (QD) with 1 cycle every 28 days. Investigator-assessed responses occurred on Day 1 of cycles 3, 5, 7 and every 3 cycles thereafter.

Primary data from February 12, 2021, show that out of 26 patients with KIT-altered melanoma, 9 had mutations in exon 11, 4 in exon 13, 11 in exon 17, 1 in exon 18, and 1 experienced KIT amplification. The median number of prior drug therapy lines was 2.

The ORR was 23% (1 complete, 5 partial responses). Median PFS was 7.3 months with a median duration of response of 7.4 months.

“Ripretinib and DP-5439 (active metabolite) plasma concentrations are generally consistent in patients with melanoma and those with GIST dosed at 150 mg QD, based on sparse pharmacokinetic sampling,” continued Dr Janku, et al.

Common drug-related, treatment-emergent adverse events (TEAEs) occurred thus far in >15% of patients were increased lipase (n = 13), alopecia (n=8), myalgia (n=5), actinic keratosis, arthralgia, decreased appetite, fatigue, nausea, and palmar-plantar erythrodysesthesia syndrome (n = 4 each).

“Preliminary results show ripretinib had a manageable safety profile and demonstrated encouraging efficacy in KIT-altered melanoma with 23% ORR and 7.3 months mPFS, indicating that ripretinib may have a role in treating this patient population,” concluded Dr Janku, et al. – Alexa Stoia