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Ref Type Abstract
PMID
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
Vol 32
Issue 5
Date September 01, 2021
URL https://www.annalsofoncology.org/article/S0923-7534(21)03696-6/fulltext
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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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
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...