Abstract 62P
Background
Ripretinib is a switch-control tyrosine kinase inhibitor approved in the US and EU for patients (pts) with gastrointestinal stromal tumor (GIST) who received prior treatment with 3 or more kinase inhibitors, including imatinib. Sunitinib is approved for advanced GIST after imatinib failure. In an exploratory analysis of baseline circulating tumor DNA (ctDNA) from the INTRIGUE trial, pts with primary mutations in KIT exon 11 and secondary mutations exclusively in KIT exons 17/18 (KIT exon 11 + 17/18) received clinical benefit from ripretinib but not sunitinib (Heinrich MC, et al. Nat Med. 2024). Here, we present final overall survival (OS) and updated safety in pts with KIT exon 11 + 17/18 mutations from INTRIGUE.
Methods
INTRIGUE (NCT03673501) is an open-label, phase 3 study of adults with advanced GIST who had disease progression on or intolerance to imatinib. Randomization was 1:1 to ripretinib 150 mg once daily (QD) or sunitinib 50 mg QD (4 wks on/2 wks off). Final OS analysis was prespecified to occur with ≥200 and ≥145 events in the all-patient intention-to-treat (ITT) and KIT exon 11 ITT populations, respectively. Baseline peripheral whole blood was analyzed by Guardant360, a 74-gene ctDNA next-generation sequencing–based assay. Data cutoff was March 15, 2023.
Results
Of 453 pts, ctDNA was analyzed in an exploratory analysis for 362; 52 had mutations exclusively in KIT exon 11 + 17/18 (ripretinib, n = 27; sunitinib, n = 25). Pts with KIT exon 11 + 17/18 mutations had better OS with ripretinib vs sunitinib (median, not reached vs 17.5 months; HR, 0.37; 95% CI, 0.17 to 0.80; nominal P = 0.0091). Fewer of these pts had grade 3/4 drug-related treatment-emergent adverse events and serious adverse events with ripretinib vs sunitinib (33% vs 50% and 3.7% vs 13%, respectively). Median treatment duration in these pts for ripretinib vs sunitinib was 15.6 vs 3.0 months.
Conclusions
In this updated exploratory analysis from INTRIGUE, OS was longer for ripretinib vs sunitinib for pts with KIT exon 11 + 17/18 mutations identified by baseline ctDNA. The safety profile was consistent and more favorable for ripretinib vs sunitinib in these pts.
Clinical trial identification
NCT03673501.
Editorial acknowledgement
Medical writing and editorial support were provided by Steven Walker, PhD, of AlphaBioCom, a Red Nucleus company, and were funded by Deciphera Pharmaceuticals, LLC.
Legal entity responsible for the study
Deciphera Pharmaceuticals, LLC and the INTRIGUE study investigators.
Funding
Deciphera Pharmaceuticals, LLC.
Disclosure
J-Y. Blay: Financial Interests, Institutional, Invited Speaker: MSD, MSD, PharmaMar; Financial Interests, Institutional, Advisory Board: Bayer, GSK, Roche; Financial Interests, Personal, Advisory Board: Deciphera; Financial Interests, Personal, Other, member of the supervisory board. No remunerations in 2021 and 2022: Innate pharma; Financial Interests, Personal, Member of Board of Directors: Transgene; Financial Interests, Institutional, Funding: MSD, BMS, Deciphera; Financial Interests, Institutional, Research Grant: AstraZeneca, Roche, Bayer, GSK, Novartis, OSE pharma. R.L. Jones: Financial Interests, Personal, Expert Testimony, I worked as a consultant: Adaptimmune, Bayer, Boehringer Ingelheim, Blueprint, Clinigen, Eisai, Epizyme, Daiichi Sankyo, Deciphera, Immunedesign, Lilly, Springworks, Tracon, Upto Date, PharmaMar; Financial Interests, Personal, Advisory Board, I worked as a consultant.: Athenex, Astex, Immunicum, Karma Oncology, Merck, Mundipharma, Synox; Financial Interests, Institutional, Research Grant, Research grant for a clinical trial: MSD. H. Gelderblom: Financial Interests, Institutional, Invited Speaker: Daiichi Sankyo, Deciphera, Novartis, Boehringer Ingelheim, AmMax Bio, Debiopharm, Cytovation, Abbisko. S. George: Financial Interests, Personal, Stocks/Shares, Stock/other ownership interests: Abott Laboratories; Non-Financial Interests, Personal, Other, Honoraria: CStone Pharmaceuticals; Financial Interests, Personal, Advisory Role, Consulting or advisory role: Blueprint Medicines, Deciphera Pharmaceuticals, LLC, Lilly, UpToDate, Research to Practice, MORE Health, Daiichi Sankyo, KayoThera, Immunicum; Financial Interests, Institutional, Funding, Research funding: Blueprint Medicines, Deciphera Pharmaceuticals, LLC, Daiichi Sankyo RD Novare, Merck; Financial Interests, Institutional, Funding, Research: Eisai, SpringWorks Therapeutics, TRACON Pharma, Theseus Pharmaceuticals, NewBay, IDRX; Financial Interests, Personal, Funding, Research: BioAtla; Financial Interests, Personal, Royalties, Patients/Royalties/Intellectual property: UptoDate; Other, Personal, Other: WCG. P. Schöffski: Financial Interests, Personal, Other, Honoraria: Blueprint Medicines; Financial Interests, Personal, Advisory Role, Consulting or advisory role: Deciphera Pharmaceuticals, LLC, Ellipses Pharma, Blueprint Medicines, Transgene, Exelixis, Boehringer Ingelheim, Studiecentrum voor Kernenergie (SCK CEN), SQZ Biotechnology, Adcendo, PharmaMar, Merck, Medpace; Financial Interests, Institutional, Funding, Research funding: CoBioRes NV, Eisai, G1 Therapeutics, PharmaMar, Genmab, Merck, Sartar Therapeutics, ONA Therapeutics. M. von Mehren: Financial Interests, Personal, Advisory Role, Consulting or advisory role: Deciphera Pharmaceuticals, LLC, GSK; Financial Interests, Institutional, Funding, Research funding: Novartis, Deciphera, LLC, Gradalis, Genmab, ASCO, Solaris Health; Financial Interests, Personal, Royalties, Patents/Royalties/other intellectual property: Cell line; Other, Personal, Other, Other relationship: NCCN. J.R. Zalcberg: Non-Financial Interests, Personal, Leadership Role: ICON Group; Financial Interests, Personal, Stocks/Shares, Stock/other ownership interests: Biomarin, Opthea, Amarin Corporation, Concert Pharmaceuticals, Frequency Therapeutics, Gilead Sciences, Madrigal Pharmaceuticals, UniQure, Zogenix, Orphazyme, Moderna Therapeutics, Twist Bioscience, Novavax; Financial Interests, Personal, Other, Honoraria: Specialised Therapeutics, Merck Serono, Targovax, Halozyme, Gilead Sciences, Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Advisory Role, Consulting or advisory role: Merck Serono, Targovax, Merck Sharp & Dohme, Halozyme, Lipotek, Specialised Therapeutics, Center for Emerging & Neglected Diseases (CEND), Deciphera Pharmaceuticals, LLC, Revolution Medicine, FivePHusion, Genor BioPharma, 1Globe Health Institute, Novotech; Financial Interests, Institutional, Funding, Research funding: Merck Serono, Bristol Myers Squibb, AstraZeneca, Pfizer, IQVIA, Mylan, Ipsen, Eisai, Medtronic, MSD Oncology; Financial Interests, Personal, Funding, Funding for travel/accommodations/expenses: Merck Serono, AstraZeneca, Merck Sharp & Dohme, Deciphera Pharmaceuticals, LLC, Sanofi. Y. Kang: Financial Interests, Personal, Advisory Board: ALX Oncology, Zymeworks, Amgen, Novartis, Macrogenics, Daehwa, Blueprint, Surface Oncology, BMS, Merck, Roche, Liscure. A.R. Abdul Razak: Financial Interests, Personal, Advisory Role, Consulting or advisory role: Adaptimmune, Bayer, GSK, Medison, Inhibrx; Financial Interests, Personal, Funding, Research funding: Deciphera Pharmaceuticals, LLC, Karyopharm Therapeutics, Pfizer, Roche/Genentech, Bristol Myers Squibb, MedImmune, Amgen, GSK, Blueprint Medicines, Merck, AbbVie, Adaptimmune, Iterion Therapeutics, Neoleukin Therapeutics, Daiichi Sankyo, Symphogen, Rain Therapeutics; Non-Financial Interests, Personal, Expert Testimony: Medison. J.C. Trent: Financial Interests, Personal, Advisory Role, Consulting or advisory role: Blueprint Medicines, Deciphera Pharmaceuticals, LLC, Daiichi Sankyo, Epizyme, Agios, C4 Therapeutics, Bayer, AADI Bioscience, LLC, Foghorn Therapeutics, Boehringer Ingelheim, Cogent Medicine, Servier. S. Attia: Financial Interests, Institutional, Funding, Research funding: AB Science, TRACON Pharma, Bayer, Novartis, Lilly, Immune Design, Karyopharm Therapeutics, Epizyme, Blueprint Medicines, Genmab, CBA Pharma, Desmoid Tumor Research Foundation, Merck, Philogen, Gradalis, Deciphera Pharmaceuticals, LLC, Takeda, Incyte, SpringWorks Therapeutics, Adaptimmune, Advenchen Laboratories, Bavarian Nordic, BTG, PTC Therapeutics, GSK, FORMA Therapeutics, Ayala Pharmaceuticals, Trillium Therapeutics, Boehringer Ingelheim, Salarius Pharmaceuticals, Theseus Pharmaceuticals, Monopar Therapeutics, C4 Therapeutics, InhibRx, Noxopharm, Rain Therapeutics. A. Le Cesne: Financial Interests, Personal, Other, Honoraria: Bayer, PharmaMar, Deciphera Pharmaceuticals, LLC. E. Davis: Financial Interests, Personal, Stocks/Shares, Stock ownership: Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals, LLC. K. Sprott: Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Full or part-time Employment, For immediate family member not self: Stablix; Financial Interests, Personal, Stocks/Shares, Stock and other ownership: Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Stocks/Shares, Stock and other ownership for immediate family member: Stablix. P. Cox: Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Stocks/Shares, Stock and other ownership interests: Deciphera Pharmaceuticals, LLC. M.L. Sherman: Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Member of Board of Directors: Pieris Pharmaceuticals; Financial Interests, Personal, Leadership Role: Deciphera Pharmaceuticals, LLC, Pieris Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Deciphera Pharmaceuticals, LLC, Pieris Pharmaceuticals; Financial Interests, Personal, Royalties, Patents/royalties/other intellectual property: Acceleron Pharma. R. 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Heinrich: Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Advisory Role, Consulting or advisory role: Blueprint Medicines, Novartis, Theseus Pharmaceuticals, Deciphera Pharmaceuticals, LLC; Financial Interests, Institutional, Royalties, Patents/royalties/other intellectual property licensed to Novartis: Novartis; Financial Interests, Personal, Research Grant, Partial salary from a research grant from the Jonathan DavidFoundation, a VA Merit Review Grant (I01BX005358): Jonathan David Foundation; Financial Interests, Personal, Research Grant, Partial salary from a research grant from an NCI R21 grant (R21CA263400): NCI. S. Bauer: Financial Interests, Personal, Other, Honoraria: Bayer, GSK, Novartis, Pfizer, PharmaMar, Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Advisory Role, Consulting or advisory role: ADC Therapeutics, Adcendo, Bayer, Blueprint Medicines, Boehringer Ingelheim, Daiichi Sankyo, Exelixis, GSK, Janssen-Cilag, Lilly, Mundipharma, Deciphera Pharmaceuticals, LLC, Nanobiotix; Financial Interests, Personal, Funding, Research funding: Blueprint Medicines, Novartis; Financial Interests, Institutional, Funding, Research funding: Incyte; Financial Interests, Personal, Funding, Funding for travel/accommodations/expenses: PharmaMar.