Abstract 1082P
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.
Editorial acknowledgement
Editorial writing support was provided by Helen Rodgers, PhD, of AlphaBioCom, LLC, King of Prussia, PA.
Legal entity responsible for the study
Deciphera Pharmaceuticals, LLC.
Funding
Deciphera Pharmaceuticals, LLC.
Disclosure
F. Janku: Financial Interests, Personal, Stocks/Shares, Ownership interests: Cardiff Oncology; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: BioMed Valley Discoveries; Financial Interests, Institutional, Research Grant: Astex; Financial Interests, Institutional, Research Grant: Agios; Financial Interests, Institutional, Research Grant: Bicara; Financial Interests, Institutional, Research Grant: Bioxcel Therapeutics; Financial Interests, Institutional, Research Grant: FORE; Financial Interests, Institutional, Research Grant: Deciphera; Financial Interests, Institutional, Research Grant: Symphogen; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: Asana; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Ideaya Biosciences; Financial Interests, Institutional, Research Grant: JS InnoPharm; Financial Interests, Institutional, Research Grant: Synthorx; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: F-star Therapeutics; Financial Interests, Institutional, Research Grant: SQZ Biotechnologies; Financial Interests, Institutional, Research Grant: Synlogic; Financial Interests, Institutional, Research Grant: FujiFilm Pharmaceuticals; Financial Interests, Institutional, Research Grant: Sotio; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Puretech Health; Financial Interests, Personal, Advisory Role: Bicara; Financial Interests, Personal, Advisory Role: Illumina; Financial Interests, Personal, Advisory Role: Ideaya Biosciences; Financial Interests, Personal, Advisory Role: IFM Therapeutics; Financial Interests, Personal, Advisory Role: Synlogic; Financial Interests, Personal, Advisory Role: Sotio; Financial Interests, Personal, Advisory Role: Puretech Health; Financial Interests, Personal, Advisory Role: Petra Pharma; Financial Interests, Personal, Advisory Role: FORE; Financial Interests, Personal, Advisory Role: Deciphera; Financial Interests, Personal, Advisory Role: Cardiff Oncology; Financial Interests, Personal, Advisory Role: Immunomet; Financial Interests, Institutional, Research Grant: NextCure. S. Bauer: Financial Interests, Personal and Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: Blueprint Medicines; Financial Interests, Personal, Advisory Role: Blueprint Medicines; Financial Interests, Personal, Advisory Role: ADC Therapeutics; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Plexxikon; Financial Interests, Personal, Advisory Role: Nanobiotix; Financial Interests, Personal, Advisory Role: Deciphera; Financial Interests, Personal, Advisory Role: Exelixis; Financial Interests, Personal, Advisory Role: Janssen-Cilag; Financial Interests, Personal, Advisory Role: Pharmamar; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Bayer; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: Pharmamar; Non-Financial Interests, Personal, Advisory Board, Member of external advisory board for \"Off label use in oncology\": Federal Ministry of Health . K. Shoumariyeh: Financial Interests, Personal, Other, Honoraria, Travel/Accommodation/Expenses: Novartis; Financial Interests, Personal, Other, Honoraria: Blueprint Medicines; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Blueprint Medicines; Financial Interests, Personal, Other, Travel/Accomodation/Expenses: AbbVie. R.L. Jones: Financial Interests, Institutional, Research Grant, Clinical Trial: MSD; Financial Interests, Personal, Advisory Role: Adaptimmune; Financial Interests, Personal, Advisory Role: Athenex; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Blueprint; Financial Interests, Personal, Advisory Role: Clinigen; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Epizyme; Financial Interests, Personal, Advisory Role: Daiichi; Financial Interests, Personal, Advisory Role: Deciphera; Financial Interests, Personal, Advisory Role: Immunedesign; Financial Interests, Personal, Advisory Role: Lilly; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Pharmamar; Financial Interests, Personal, Advisory Role: Springworks; Financial Interests, Personal, Advisory Role: Tracon; Financial Interests, Personal, Advisory Role: Upto Date; Financial Interests, Personal, Other, Honoraria: Adaptimmune; Financial Interests, Personal, Other, Honoraria: Athenex; Financial Interests, Personal, Other, Honoraria: Bayer; Financial Interests, Personal, Other, Honoraria: Boehringer Ingelheim; Financial Interests, Personal, Other, Honoraria: Blueprint; Financial Interests, Personal, Other, Honoraria: Clinigen; Financial Interests, Personal, Other, Honoraria: Eisai; Financial Interests, Personal, Other, Honoraria: Epizyme; Financial Interests, Personal, Other, Honoraria: Daiichi; Financial Interests, Personal, Other, Honoraria: Deciphera; Financial Interests, Personal, Other, Honoraria: Immunedesign; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: Merck; Financial Interests, Personal, Other, Honoraria: Pharmamar; Financial Interests, Personal, Other, Honoraria: Springworks; Financial Interests, Personal, Other, Honoraria: Tracon; Financial Interests, Personal, Other, Honoraria: Upto Date. A. Spreafico: Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Oncorus; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Bristol-Myers Squibb; Financial Interests, Institutional, Research Grant: Symphogen; Financial Interests, Institutional, Research Grant: AstraZeneca/MedImmune; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Surface Oncology; Financial Interests, Institutional, Research Grant: Northern Biologics; Financial Interests, Institutional, Research Grant: Janssen Oncology/Johnson & Johnson; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Regeneron; Financial Interests, Institutional, Research Grant: Alkermes; Financial Interests, Institutional, Research Grant: Array Biopharma/Pfizer; Financial Interests, Institutional, Research Grant: Treatwell; Financial Interests, Institutional, Research Grant: GSK. J. Jennings: Financial Interests, Personal, Full or part-time Employment: Deciphera. C. Psoinos: Financial Interests, Personal, Stocks/Shares: AbbVie Inc; Financial Interests, Personal, Stocks/Shares: Amazon; Financial Interests, Personal, Stocks/Shares: British American Tobacco PLC; Financial Interests, Personal, Stocks/Shares: CVS Health Corp; Financial Interests, Personal, Stocks/Shares: Walt Disney Co; Financial Interests, Personal, Stocks/Shares: Consolidated Edison, Inc.; Financial Interests, Personal, Stocks/Shares: General Electric Company; Financial Interests, Personal, Stocks/Shares: General Mills, Inc.; Financial Interests, Personal, Stocks/Shares: Johnson & Johnson; Financial Interests, Personal, Stocks/Shares: Kellogg Company; Financial Interests, Personal, Stocks/Shares: Kimberly Clark Corp; Financial Interests, Personal, Stocks/Shares: Kinder Morgan Inc.; Financial Interests, Personal, Stocks/Shares: Lockheed Martin Corporation; Financial Interests, Personal, Stocks/Shares: Main Street Capital Corporation; Financial Interests, Personal, Stocks/Shares: McCormick & Company, Incorporated; Financial Interests, Personal, Stocks/Shares: 3M Co; Financial Interests, Personal, Stocks/Shares: Altria Group Inc.; Financial Interests, Personal, Stocks/Shares: NextEra Energy Inc.; Financial Interests, Personal, Stocks/Shares: Northrop Grumman Corporation; Financial Interests, Personal, Stocks/Shares: Realty Income Corp; Financial Interests, Personal, Stocks/Shares: PepsiCo, Inc.; Financial Interests, Personal, Stocks/Shares: Pfizer Inc.; Financial Interests, Personal, Stocks/Shares: Public Storage; Financial Interests, Personal, Stocks/Shares: Starbucks Corporation; Financial Interests, Personal, Stocks/Shares: Stag Industrial Inc; Financial Interests, Personal, Stocks/Shares: AT&T Inc.; Financial Interests, Personal, Stocks/Shares: Molson Coors Beverage Co Class B; Financial Interests, Personal, Stocks/Shares: Viatris Inc; Financial Interests, Personal, Sponsor/Funding: Verizon Communications Inc.; Financial Interests, Personal, Stocks/Shares: WP Carey Inc; Financial Interests, Personal, Stocks/Shares: Exxon Mobil Corporation; Financial Interests, Personal, Full or part-time Employment: Deciphera. J. Meade: Financial Interests, Personal, Stocks/Shares: Deciphera; Financial Interests, Personal, Full or part-time Employment: Deciphera. R. Ruiz-Soto: Financial Interests, Personal, Stocks/Shares: Deciphera; Financial Interests, Personal, Full or part-time Employment: Deciphera. P. Chi: Financial Interests, Personal, Advisory Role: Deciphera; Financial Interests, Personal, Advisory Role: Exelixis; Financial Interests, Personal, Advisory Role: ZaiLab; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: NewBay; Financial Interests, Institutional, Research Grant: Deciphera; Financial Interests, Institutional, Research Grant: Pfizer/Array; Other, Personal, Other, Spouse/Financial Dependent: Oric Pharma.