1622MO - Clinical benefit with ripretinib as ≥4th line treatment in patients with advanced gastrointestinal stromal tumors (GIST): Update from the phase III INVICTUS study

Background

Ripretinib is an FDA-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 ≥4^th-line advanced GIST, ripretinib compared with placebo (PBO) significantly improved progression-free survival (PFS, 6.3 vs. 1.0 months) reducing the risk of disease progression or death by 85% and showed a clinically meaningful improvement in overall survival (OS, 15.1 vs 6.6 months); data as of May 31, 2019 (ESMO 2019). Ripretinib is associated with a well-tolerated safety profile. Here, we report the updated results with an additional 9 months of follow-up.

Methods

Patients with advanced GIST previously treated with at least imatinib, sunitinib, and regorafenib were randomized (2:1) to ripretinib 150 mg QD or PBO. Upon disease progression determined by blinded independent central review (BICR), patients on PBO could cross over to ripretinib 150 mg QD. All patients who received 150 mg QD and progressed radiographically could receive 150 mg BID. Updated PFS by BICR, OS, and safety are reported here with data as of March 9, 2020.

Results

Overall, 129 patients were randomized and 128 received treatment (ripretinib 150 mg QD, n=85; PBO, n=43). Patients randomized to ripretinib had a median PFS (mPFS) of 6.3 (95% CI 4.6−8.1) vs. 1.0 (95% CI 0.9−1.7) months for patients on PBO with a hazard ratio (HR) of 0.16. The median OS (mOS) in the ripretinib arm was not reached (95% CI 13.1–NE) vs. 6.3 (95% CI 4.1−10.0) months in the PBO arm with a HR of 0.43. No new safety concerns emerged with longer exposure to ripretinib.

Conclusions

Evaluation of mPFS and OS in the phase III randomized INVICTUS trial, with a cut-off date for analysis approximately 9 months after the primary results, has shown an improvement in the mOS in the ripretinib arm from 15.1 months to not reached (95% CI 13.1–NE) and a similar mPFS of 6.3 months in the ripretinib arm. These updated results confirm the clinically meaningful benefit in PFS and OS for ripretinib with a well-tolerated safety profile in patients with advanced GIST treated with at least 3 prior TKIs, including imatinib.

Clinical trial identification

NCT03353753.

Editorial acknowledgement

Medical writing and editorial support were provided by Lauren Hanlon, PhD; and Stefan Kolata, PhD, of AlphaBioCom, LLC (King of Prussia, PA).

Legal entity responsible for the study

Deciphera Pharmaceuticals, LLC.

Funding

Deciphera Pharmaceuticals, LLC.

Disclosure

J.R. Zalcberg: Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Pfizer; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Merck Serono; Honoraria (self), Research grant/Funding (institution): Specialized Therapeutics; Honoraria (self), Advisory/Consultancy: Targovax; Honoraria (self), Advisory/Consultancy: Halozyme; Honoraria (self), Shareholder/Stockholder/Stock options: Gilead Sciences; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: MSD; Advisory/Consultancy, Travel/Accommodation/Expenses: Sirtex Medical; Advisory/Consultancy: Lipotek; Advisory/Consultancy: Novella; Honoraria (self), Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Roche; Research grant/Funding (institution): BMS; Research grant/Funding (institution), Travel/Accommodation/Expenses: AstraZeneca; Research grant/Funding (institution): Baxalta/Shire; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Boehringer-Ingelheim; Travel/Accommodation/Expenses: Deciphera; Travel/Accommodation/Expenses: Sirtex; Shareholder/Stockholder/Stock options: GW Pharmaceuticals; Shareholder/Stockholder/Stock options: Aimmune; Shareholder/Stockholder/Stock options: Vertex; Shareholder/Stockholder/Stock options: Bluebird Bio; Shareholder/Stockholder/Stock options: Alnylam; Shareholder/Stockholder/Stock options: Biomarin; Shareholder/Stockholder/Stock options: Sage Therapeutics; Shareholder/Stockholder/Stock options: Dova Pharmaceuticals; Shareholder/Stockholder/Stock options: Therapeutics MD; Shareholder/Stockholder/Stock options: Juno Therapeutics; Shareholder/Stockholder/Stock options: Kite Pharma; Shareholder/Stockholder/Stock options: Kiadis Pharma; Shareholder/Stockholder/Stock options: CSL Limited; Shareholder/Stockholder/Stock options: Cochlear; Non-remunerated activity/ies, Chair: Australian Clinical Trials Alliance; Non-remunerated activity/ies, Co-chair: National Oncology Alliance; Non-remunerated activity/ies, Co-chair: All.Can Australia; Shareholder/Stockholder/Stock options: Amarin; Shareholder/Stockholder/Stock options: Freq Therapeutics; Shareholder/Stockholder/Stock options: Global Blood Therapeutics; Shareholder/Stockholder/Stock options: Uniqure; Shareholder/Stockholder/Stock options: Sangamo; Shareholder/Stockholder/Stock options: Acceleron; Shareholder/Stockholder/Stock options: Zogenix. M. Heinrich: Advisory/Consultancy, Speaker Bureau/Expert testimony, Licensing/Royalties, Expert Testimony: Novartis; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Deciphera; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Blueprint; Advisory/Consultancy: MolecularMD. S. George: Advisory/Consultancy, Research grant/Funding (institution): Blueprint Medicines; Advisory/Consultancy, Research grant/Funding (institution): Deciphera; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Bayer; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Exelixis; Leadership role: Alliance Foundation; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Novartis; Shareholder/Stockholder/Stock options: Abbott Labs; Shareholder/Stockholder/Stock options: Allergan; Licensing/Royalties, UpToDate: Wolters Kluwer Health. S. Bauer: Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Research grant/Funding (institution): Novartis; Honoraria (self): Pfizer; Honoraria (self), Advisory/Consultancy: Bayer; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: Pharmamar; Advisory/Consultancy, Research grant/Funding (institution): Blueprint Medicines; Advisory/Consultancy: ADC Therapeutics; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Plexxikon; Advisory/Consultancy: Nanobiotix; Advisory/Consultancy: Deciphera; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Janssen-Cilag; Advisory/Consultancy: Roche; Research grant/Funding (institution): Incyte; Non-remunerated activity/ies, Member of external advisory board for \"off-label use in oncology\": Federal Ministry of Health. H. Gelderblom: Research grant/Funding (institution): Daiichi; Research grant/Funding (institution): Five Prime; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Deciphera; Research grant/Funding (institution): Lilly; Research grant/Funding (institution): Roche; Research grant/Funding (institution): Eisai; Research grant/Funding (institution): Debio; Research grant/Funding (institution): Boehringer; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Amgen; Research grant/Funding (institution): TEVA. P. Schöffski: Advisory/Consultancy, Research grant/Funding (institution): Plexxikon; Advisory/Consultancy, Research grant/Funding (institution): Eisai; Advisory/Consultancy: Loxo; Advisory/Consultancy, Research grant/Funding (institution): Lilly; Honoraria (self), Advisory/Consultancy, Research grant/Funding (institution): Blueprint Medicines; Advisory/Consultancy: Ellipses Pharma; Advisory/Consultancy: Deciphera; Advisory/Consultancy: Merck; Advisory/Consultancy: Servier; Advisory/Consultancy: Genmab; Advisory/Consultancy: Adaptimmune; Advisory/Consultancy: Intellisphere LLC; Advisory/Consultancy: Transgene; Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): CoBioRes NV; Research grant/Funding (institution): Exelixis; Research grant/Funding (institution): G1 Therapeutics; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Pharmamar. C. Serrano: Advisory/Consultancy, Research grant/Funding (self): Deciphera; Advisory/Consultancy, Speaker Bureau/Expert testimony: Blueprint Medicines; Speaker Bureau/Expert testimony, Research grant/Funding (self), Travel/Accommodation/Expenses: Bayer Healthcare; Research grant/Funding (self), Travel/Accommodation/Expenses: Pfizer; Travel/Accommodation/Expenses: Pharmamar; Travel/Accommodation/Expenses: Novartis; Travel/Accommodation/Expenses: Lilly. R.L. Jones: Honoraria (self), Advisory/Consultancy: Adaptimmune; Honoraria (self), Advisory/Consultancy: Athenex; Honoraria (self), Advisory/Consultancy: Blueprint; Honoraria (self), Advisory/Consultancy: Clinigen; Honoraria (self), Advisory/Consultancy: Eisai; Honoraria (self), Advisory/Consultancy: Epizyme; Honoraria (self), Advisory/Consultancy: Daiichi; Honoraria (self), Advisory/Consultancy: Deciphera; Honoraria (self), Advisory/Consultancy: Immunedesign; Honoraria (self), Advisory/Consultancy: Lilly; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: Pharmamar; Honoraria (self), Advisory/Consultancy: Upto Date; Advisory/Consultancy: Tracon; Research grant/Funding (institution), Clinical trial: MSD. S. Attia: Research grant/Funding (self): Desmoid Tumor Research Foundation; Research grant/Funding (institution): AB Science; Research grant/Funding (institution): Tracon Pharma; Research grant/Funding (institution): CytRx Corporation; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Daiichi Sankyo; Research grant/Funding (institution): Lilly; Research grant/Funding (institution), Travel/Accommodation/Expenses: Immune Design; Research grant/Funding (institution): Karyopharm Therapeutics; Research grant/Funding (institution): Epizyme; Research grant/Funding (institution): Blueprint Medicines; Research grant/Funding (institution): Genmab; Research grant/Funding (institution): CBA Pharma; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Philogen; Research grant/Funding (institution): Gradalis; Research grant/Funding (institution): Deciphera; Research grant/Funding (institution): Takeda; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): Springworks; Research grant/Funding (institution): Adaptimmune; Research grant/Funding (institution): Advenchen Laboratories; Research grant/Funding (institution): Bavarian Nordic; Research grant/Funding (institution): BTG; Research grant/Funding (institution): PTC Therapeutics; Research grant/Funding (institution): GlaxoSmithKline; Research grant/Funding (institution): FORMA Therapeutics. G. D'Amato: Advisory/Consultancy, Speaker Bureau/Expert testimony: Lilly Pharmaceuticals; Advisory/Consultancy: Blueprint; Advisory/Consultancy, Speaker Bureau/Expert testimony: Janssen; Speaker Bureau/Expert testimony: Eisai; Advisory/Consultancy: Deciphera. P. Chi: Advisory/Consultancy, Research grant/Funding (institution), Clinical Research Support: Deciphera; Advisory/Consultancy: Exelixis; Research grant/Funding (institution), Clinical Research Support: Novartis; Research grant/Funding (institution), Clinical Research Support: Array. P. Reichardt: Honoraria (self), Research grant/Funding (institution): Novartis; Honoraria (self): Pfizer; Honoraria (self): PharmaMar; Honoraria (self): Lilly; Honoraria (self): Amgen; Advisory/Consultancy: Clinigen Group; Advisory/Consultancy: Roche; Advisory/Consultancy: Bayer; Advisory/Consultancy: Deciphera; Advisory/Consultancy: MSD; Advisory/Consultancy: Bristol-Myers Squibb. J.N. Meade: Travel/Accommodation/Expenses, Shareholder/Stockholder/Stock options, Full/Part-time employment, Sponser (of study) full time employee; granted stock options as a full time employee and sponser of study: Deciphera. V. Reichert: Shareholder/Stockholder/Stock options, Full/Part-time employment: Deciphera. K. Shi: Shareholder/Stockholder/Stock options: Alnylam; Shareholder/Stockholder/Stock options: Immunogen; Shareholder/Stockholder/Stock options: Karyopharm; Full/Part-time employment: Deciphera. R. Ruiz-Soto: Shareholder/Stockholder/Stock options, Full/Part-time employment, Employee: Deciphera. M. von Mehren: Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses: Deciphera; Advisory/Consultancy, Research grant/Funding (institution): Blueprint; Advisory/Consultancy: Exelexis; Research grant/Funding (institution): Arog; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Gradalis; Research grant/Funding (institution): GenMab; Travel/Accommodation/Expenses: NCCN. J-Y. Blay: Honoraria (self), Honoraria (institution), Advisory/Consultancy: Novartis; Honoraria (self), Honoraria (institution), Advisory/Consultancy: Bayer; Honoraria (self), Honoraria (institution), Advisory/Consultancy: Pfizer; Honoraria (self), Honoraria (institution), Advisory/Consultancy: Deciphera; Honoraria (self), Honoraria (institution), Advisory/Consultancy: Roche.