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|Authors||F. Janku S. Bauer K. Shoumariyeh R.L. Jones A. Spreafico J. Jennings C. Psoinos J. Meade R. Ruiz-Soto P. Chi|
|Title||1082P Phase I study of ripretinib, a broad-spectrum KIT and PDGFRA inhibitor, in patients with KIT-mutated or KIT-amplified melanoma|
|Journal||Annals of Oncology|
|Date||September 01, 2021|
|Abstract Text||Background Ripretinib, a kinase switch-control inhibitor designed to broadly inhibit KIT and PDGFRA mutations, is indicated in the treatment of adult patients (pts) with advanced gastrointestinal stromal tumor (GIST) who have received 3 or more prior tyrosine kinase inhibitors (TKIs), including imatinib. We present results of the KIT-altered (mutated or amplified) melanoma cohort in an ongoing phase I trial (NCT02571036). 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; however, reported objective response rate (ORR) is typically <20% and progression-free survival (PFS) 3–4 months. Methods In the expansion arm of this phase I study, pts with KIT-altered melanoma were treated with ripretinib at the recommended phase II dose of 150 mg once daily (QD) (1 cycle every 28 days). Investigator-assessed responses were performed on Day 1 of Cycles 3, 5, 7, and every 3 cycles thereafter. Results As of February 12, 2021, of 26 pts enrolled with KIT-altered melanoma, 9 pts had mutations in exon 11, 4 in exon 13, 11 in exon 17, 1 in exon 18, and 1 had a KIT amplification. The median number of prior drug therapy lines was 2. Confirmed 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 pts with melanoma and those with GIST dosed at 150 mg QD, based on sparse pharmacokinetic sampling. The most common drug-related treatment-emergent adverse events (TEAEs; any grade) occurring 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). The only drug-related Grade 3 TEAE occurring in >5% of patients was increased lipase (n = 8). There were no Grade ≥4 drug-related TEAEs. Conclusions 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 these pts. Clinical trial identification NCT02571036.|
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|KIT mutant||melanoma||predicted - sensitive||Ripretinib||Phase I||Actionable||In a Phase I trial, Qinlock (ripretinib) treatment demonstrated manageable safety and preliminary efficacy in patients with KIT-mutated melanoma, and led to an objective response rate of 23% (6/26, 1 complete and 5 partial responses), a median progression-free survival of 7.3 months, and a median duration of response of 7.4 months (Annals of Oncology 32 (2021): S896-S897; NCT02571036).||detail...|