Abstract 1540P
Background
Ripretinib is an approved switch-control tyrosine kinase inhibitor (TKI) that broadly inhibits mutant KIT and PDGFRA kinase signaling. In INVICTUS, a randomized, double-blind, placebo-controlled trial in ≥4th-line advanced GIST, ripretinib compared with placebo (PBO) significantly improved median progression-free survival (mPFS; 6.3 vs 1.0 months), reducing the risk of disease progression or death by 85%, and showed a clinically meaningful improvement in median overall survival (mOS; 15.1 vs 6.6 months); data as of May 31, 2019 (ESMO 2019). Ripretinib is well tolerated. Here, we present a long-term update of mature data, with a data cut-off date 19 months after the data cut-off date of the primary analysis.
Methods
Patients with advanced GIST previously treated with at least imatinib, sunitinib, and regorafenib were randomized (2:1) to ripretinib 150 mg once daily (QD) or PBO. Upon disease progression determined by blinded independent central review, patients on PBO could cross over to ripretinib 150 mg QD. All patients who received 150 mg QD and had radiological progression could receive 150 mg twice daily.
Results
As of January 15, 2021, of 129 patients randomized, 128 received treatment (ripretinib 150 mg QD, n = 85; PBO, n = 43). Patients randomized to ripretinib had a mPFS of 6.3 months (95% CI 4.6−8.1) vs 1.0 (95% CI 0.9−1.7) month for patients on PBO with a hazard ratio (HR) of 0.16. The mOS in the ripretinib arm was 18.2 months (95% CI 13.1–30.7) vs 6.3 (95% CI 4.1−10.0) months in the PBO arm with a HR of 0.41. No new safety concerns were identified with longer exposure to ripretinib.
Conclusions
Evaluation of primary and secondary endpoints in the phase 3 INVICTUS trial, with a cutoff date 19 months after the primary analysis, demonstrate stable mPFS with no change since the primary data release, and improved mOS for patients randomized to ripretinib. These more mature data continue to support the clinically meaningful benefit in PFS and OS for ripretinib with an acceptable safety profile in patients with advanced GIST treated with 3 or more prior TKIs.
Clinical trial identification
NCT03353753.
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
M. von Mehren: Financial Interests, Personal, Advisory Role: Deciphera; Financial Interests, Personal, Advisory Role: Blueprint; Financial Interests, Personal, Advisory Role: Exelis; Financial Interests, Personal and Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Deciphera; Financial Interests, Institutional, Research Grant: Blueprint; Financial Interests, Institutional, Research Grant: Arog; Financial Interests, Institutional, Research Grant: Gradalis; Financial Interests, Institutional, Research Grant: GenMab; Financial Interests, Institutional, Research Grant: ASCO; Financial Interests, Personal, Other, Travel/Accomodations/Expenses: Deciphera; Financial Interests, Personal, Other, Travel/Accomodations/Expenses: NCCN. M.C. Heinrich: Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Deciphera; Financial Interests, Personal, Advisory Role: Blueprint; Financial Interests, Personal, Advisory Role: MolecularMD; Financial Interests, Personal, Expert Testimony: Novartis; Financial Interests, Institutional, Research Grant: Blueprint; Financial Interests, Institutional, Research Grant: Deciphera; Financial Interests, Personal, Other, Travel/Accomodation/Expenses: Blueprint; Financial Interests, Personal, Other, Travel/Accomodation/Expenses: Deciphera; Financial Interests, Personal, Licensing Fees: Novartis. S. George: Financial Interests, Personal, Advisory Role: Deciphera Pharmaceuticals; Financial Interests, Personal, Advisory Role: Blueprint Medicines; Financial Interests, Personal, Advisory Role: Eli Lilly; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Exelixis; Other, Personal, Leadership Role, VP: Alliance for Clinical Trials in Oncology Foundation; Financial Interests, Institutional, Research Grant: Blueprint Medicines; Financial Interests, Institutional, Research Grant: Deciphera Pharmaceuticals; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Springworks; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Personal, Stocks/Shares: Abbott Labs; Financial Interests, Personal, Stocks/Shares: Allergan; Financial Interests, Personal, Licensing Fees, UpToDate: Wolters Kluwer Health; Financial Interests, Personal, Member of the Board of Directors: Alliance for Clinical Trials in Oncology Foundation. J.R. Zalcberg: Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: Merck Serono; Financial Interests, Personal, Other, Honoraria: Specialized Therapeutics; Financial Interests, Personal, Other, Honoraria: Targovax; Financial Interests, Personal, Other, Honoraria: Halozyme; Financial Interests, Personal, Other, Honoraria: Gilead Sciences; Financial Interests, Personal, Other, Honoraria: Bayer; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Merck Serono; Financial Interests, Personal, Advisory Role: Targovax; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Sirtex Medical; Financial Interests, Personal, Advisory Role: Halozyme; Financial Interests, Personal, Advisory Role: Lipotek; Financial Interests, Personal, Advisory Role: Novella; Financial Interests, Personal, Advisory Role: CEND; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Merck Serono; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Specialized Therapeutics; Financial Interests, Institutional, Research Grant: Baxalta/Shire; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Boehringer-Ingelheim; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Ipsen; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Merck Serono; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: AstraZeneca; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: MSD; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Deciphera; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Sirtex; Financial Interests, Personal, Stocks/Shares: GW Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Aimmune; Financial Interests, Personal, Stocks/Shares: Vertex; Financial Interests, Personal, Stocks/Shares: Bluebird Bio; Financial Interests, Personal, Stocks/Shares: Alnylam; Financial Interests, Personal, Stocks/Shares: Biomarin; Financial Interests, Personal, Stocks/Shares: Sage Therapeutics; Financial Interests, Personal, Stocks/Shares: Dova Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Therapeutics MD; Financial Interests, Personal, Stocks/Shares: Juno Therapeutics; Financial Interests, Personal, Stocks/Shares: Kite Pharma; Financial Interests, Personal, Stocks/Shares: Kiadis Pharma; Financial Interests, Personal, Stocks/Shares: CSL limited; Financial Interests, Personal, Stocks/Shares: Cochlear; Financial Interests, Personal, Stocks/Shares: Amarin; Financial Interests, Personal, Stocks/Shares: Freq Therapeutics; Financial Interests, Personal, Stocks/Shares: Global Blood Therapeutics; Financial Interests, Personal, Stocks/Shares: Gilead; Financial Interests, Personal, Stocks/Shares: Uniqure; Financial Interests, Personal, Stocks/Shares: Sangamo; Financial Interests, Personal, Stocks/Shares: Acceleron; Financial Interests, Personal, Stocks/Shares: Zogenix; Financial Interests, Personal, Stocks/Shares: Moderna; Financial Interests, Personal, Stocks/Shares: Concert; Financial Interests, Personal, Stocks/Shares: Madrigal; Financial Interests, Personal, Stocks/Shares: Myovant; Financial Interests, Personal, Stocks/Shares: Novo nordisk; Financial Interests, Personal, Member of the Board of Directors: Praxis; Non-Financial Interests, Personal, Leadership Role, Chair: Australian Clinical Trials Alliance; Non-Financial Interests, Personal, Leadership Role, Co-Chair: National Oncology Alliance; Non-Financial Interests, Personal, Leadership Role, Co-Chair: All.Can Australia. S. Bauer: 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; 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 and Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: Blueprint Medicines; Non-Financial Interests, Personal, Advisory Board, for \"Off-label use in oncology\" : Federal Ministry of Health. H. Gelderblom: Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Five Prime Therapeutics; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Non-Financial Interests, Personal, Other: Deciphera; Non-Financial Interests, Personal, Other: Lilly; Non-Financial Interests, Personal, Other: Roche; Non-Financial Interests, Personal, Other: Eisai; Non-Financial Interests, Personal, Other: Debio; Non-Financial Interests, Personal, Other: Teva. P. Schöffski: Financial Interests, Personal, Advisory Role: Blueprint Medicines; Financial Interests, Personal, Advisory Role: Ellipses Pharma; Financial Interests, Personal, Advisory Role: Deciphera; Financial Interests, Personal, Advisory Role: Intellisphere LLC; Financial Interests, Personal, Advisory Role: Transgene; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim; Financial Interests, Personal, Advisory Role: Exelixis; Financial Interests, Personal, Advisory Role: Guided Clarity; Financial Interests, Personal, Advisory Role: Medscape; Financial Interests, Personal, Advisory Role: Ysios; Financial Interests, Personal, Expert Testimony: Advanced Medical; Financial Interests, Institutional, Research Grant: CoBioRes NV; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: G1 Therapeutics; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: PharmaMar. C. Serrano: Financial Interests, Personal, Advisory Role: Deciphera Pharmaceuticals; Financial Interests, Personal, Advisory Role: Blueprint Medicines; Financial Interests, Personal, Advisory Role: Immunicum AB; Financial Interests, Personal, Speaker’s Bureau: Bayer Healthcare; Financial Interests, Personal, Speaker’s Bureau: Blueprint Medicines; Financial Interests, Institutional, Research Grant: Deciphera Pharmaceuticals; Financial Interests, Institutional, Research Grant: Bayer Healthcare; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Personal, Other, Travel/Accomodation/Expenses: Pharmamar; Financial Interests, Personal, Other, Travel/Accomodation/Expenses: Pfizer; Financial Interests, Personal, Other, Travel/Accomodation/Expenses: Bayer Healthcare; Financial Interests, Personal, Other, Travel/Accomodation/Expenses: Novartis; Financial Interests, Personal, Other, Travel/Accomodation/Expenses: Lilly. R.L. Jones: 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: UptoDate; 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: UptoDate; Financial Interests, Institutional, Research Grant, Clinical Trial: MSD. S. Attia: Financial Interests, Personal and Institutional, Research Grant: Desmoid Tumor Research Foundation; Financial Interests, Institutional, Research Grant: AB Science; Financial Interests, Institutional, Research Grant: TRACON Pharma; Financial Interests, Institutional, Research Grant: CytRx Corporation; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Immune Design; Financial Interests, Institutional, Research Grant: Karyopharm Therapeutics; Financial Interests, Institutional, Research Grant: Epizyme; Financial Interests, Institutional, Research Grant: Blueprint Medicines; Financial Interests, Institutional, Research Grant: Genmab; Financial Interests, Institutional, Research Grant: CBA Pharma; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Philogen; Financial Interests, Institutional, Research Grant: Gradalis; Financial Interests, Institutional, Research Grant: Deciphera; Financial Interests, Institutional, Research Grant: Takeda; Financial Interests, Institutional, Research Grant: Incyte; Financial Interests, Institutional, Research Grant: Springworks; Financial Interests, Institutional, Research Grant: Adaptimmune; Financial Interests, Institutional, Research Grant: Advenchen Laboratories; Financial Interests, Institutional, Research Grant: Bavarian Nordic; Financial Interests, Institutional, Research Grant: BTG; Financial Interests, Institutional, Research Grant: PTC Therapeutics; Financial Interests, Institutional, Research Grant: GlaxoSmithKline; Financial Interests, Institutional, Research Grant: FORMA Therapeutics. G. D'Amato: Financial Interests, Personal, Advisory Role: Lilly Pharmaceuticals; Financial Interests, Personal, Advisory Role: Blueprint; Financial Interests, Personal, Advisory Role: Janssen; Financial Interests, Personal, Advisory Role: Deciphera; Financial Interests, Personal, Advisory Role: Epizyme; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Speaker’s Bureau: Lilly; Financial Interests, Personal, Speaker’s Bureau: Janssen; Financial Interests, Personal, Speaker’s Bureau: Eisai. 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. P. Reichardt: Financial Interests, Personal, Other, Honoraria: Novartis; Financial Interests, Personal, Other, Honoraria: Pfizer; Financial Interests, Personal, Other, Honoraria: PharmaMar; Financial Interests, Personal, Other, Honoraria: Lilly; Financial Interests, Personal, Other, Honoraria: Amgen; Financial Interests, Personal, Advisory Role: Clinigen Group; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Deciphera; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Role: Blueprint; Financial Interests, Institutional, Research Grant: Novartis. J.N. Meade: Financial Interests, Personal, Stocks/Shares: Deciphera; Financial Interests, Personal, Full or part-time Employment: Deciphera. V.L. Reichert: Financial Interests, Personal, Stocks/Shares: Deciphera; Financial Interests, Personal, Full or part-time Employment: Deciphera. K. Shi: Financial Interests, Personal, Stocks/Shares: Alnylam; Financial Interests, Personal, Stocks/Shares: Immunogen; Financial Interests, Personal, Stocks/Shares: Karyopharm; Financial Interests, Personal, Stocks/Shares: Albireo; Financial Interests, Personal, Stocks/Shares: Avidity; Financial Interests, Personal, Stocks/Shares: AstraZeneca; Financial Interests, Personal, Stocks/Shares: Spectrum; 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. J. Blay: Financial Interests, Personal and Institutional, Other, Honoraria: Novartis; Financial Interests, Personal and Institutional, Other, Honoraria: Bayer; Financial Interests, Personal and Institutional, Other, Honoraria: Pfizer; Financial Interests, Personal and Institutional, Other, Honoraria: Deciphera; Financial Interests, Personal and Institutional, Other, Honoraria: Roche; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Deciphera; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: BMS; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Member of the Board of Directors: Innate pharma; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: GSK; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Deciphera; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: BMS; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Institutional, Research Grant: AstraZeneca.