Safety, efficacy, and patient-reported outcomes (PROs) with vimseltinib in patients (pts) with tenosynovial giant cell tumor (TGCT) who received prior anti–colony-stimulating factor 1 (CSF1) therapy: Ongoing phase II study

BackgroundVimseltinib is an investigational, oral, switch-control tyrosine kinase inhibitor specifically designed to selectively and potently inhibit the CSF1 receptor (CSF1R). In the MOTION phase III trial, vimseltinib showed statistically significant and clinically meaningful improvements in the primary and all key secondary endpoints vs placebo. Here, we will report updated safety, efficacy, and PROs from cohort B of the phase II part (expansion) of an ongoing phase I/II study (NCT03069469).MethodsPts with symptomatic TGCT not amenable to surgery who had prior anti-CSF1/CSF1R therapy received vimseltinib 30 mg twice weekly (recommended phase II dose). Primary objectives were safety and tolerability. Antitumor activity was assessed by independent radiological review using Response Evaluation Criteria in Solid Tumors version 1.1. Other assessments included active range of motion and PROs: worst pain, physical function, worst stiffness, and health status.ResultsAt a prior data cutoff (June 2023), 19 pts with TGCT who received prior anti-CSF1/CSF1R therapy were enrolled in cohort B. Most pts (79%) received prior pexidartinib. Most treatment-emergent adverse events (TEAEs) were grade 1/2. Grade 3/4 TEAEs (>5% of pts) were increased creatine phosphokinase, hypertension, and eczema. There was no evidence of cholestatic hepatotoxicity or drug-induced liver injury. Median treatment duration was 7.3 months. Antitumor activity was robust (Table). Updated results will be presented, including full enrollment and 8 months of additional follow-up. Table: 1770P BOR n = 16 Week 25a n = 16 BOR b Complete response 0c 0 Partial response 7 (44) 5 (31) Stable disease 9 (56) 5 (31) Objective response rate b 7 (44) 5 (31) Data shown as n (%). Data cutoff: June 27, 2023; 16 of 19 patients had ≥1 post-baseline imaging assessment at data cutoff (efficacy evaluable). aPatients that discontinued treatment prior to or reached week 25 were included. bAssessed by IRR using RECIST v1.1. cPreviously presented complete response (ESMO 2022) was changed to partial response by IRR based on additional follow-up assessments. BOR, best overall response; IRR, independent radiological review; RECIST v1.1, Response Evaluation Criteria in Solid Tumors version 1.1. ConclusionsVimseltinib is well tolerated and demonstrates robust antitumor activity in previously treated pts with TGCT. Updated results are expected to support long-term safety and efficacy and symptomatic improvements in pts with TGCT who received prior anti-CSF1/CSF1R therapy.Clinical trial identificationNCT03069469.Editorial acknowledgementMedical 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 studyDeciphera Pharmaceuticals, LLC.FundingDeciphera Pharmaceuticals, LLC.DisclosureG. D'Amato: Financial Interests, Personal, Advisory Role: Blueprint Medicines, Epizyme, Deciphera Pharmaceuticals, LLC, Daiichi Sankyo, Lilly. A.J. Wagner: Financial Interests, Personal, Advisory Role: Daiichi Sankyo, Deciphera Pharmaceuticals, LLC; Financial Interests, Institutional, Research Funding: Daiichi Sankyo, Deciphera Pharmaceuticals, LLC. K.N. Ganjoo: Financial Interests, Personal, Advisory Role: Daiichi Sankyo, Foundation Medicine. S. Stacchiotti: Financial Interests, Personal, Advisory Board: Bayer, Daiichi, Ikena, Regeneron, NEC Oncoimmunity AS, Pharma Essentia; Financial Interests, Personal, Other, Travel Coverage to scientific conference: PharmaMar; Financial Interests, Personal, Advisory Board, Advisory board meeting: Agenus; Financial Interests, Personal, Advisory Board, Advisory board meetings: Boehringer; Financial Interests, Personal, Invited Speaker, Lectures: Gentili; Financial Interests, Personal, Advisory Board, Advisory board: Servier; Financial Interests, Institutional, Local PI: Advenchen, Deciphera, Epizyme, Daiichi Sankyo, GSK, Karyopharm, PharmaMar, SpringWorks, Hutchison MediPharma International Inc, Inhbrix; Financial Interests, Institutional, Coordinating PI: Bayer; Financial Interests, Institutional, Funding: Blueprint, Novartis; Financial Interests, Institutional, Other, Co-investigator in clinical study: Boehringer; Non-Financial Interests, Member of Board of Directors, Secretary: Connective Tissue Oncology Society; Non-Financial Interests, Advisory Role: Chordoma Foundation, Epithelioid Haemangiondothelioma Foundation, Desmoid Foundation, Epithelioid Hemangioendothelioma (EHE) Rare Cancer Charity (UK); Non-Financial Interests, Other, Secretary: EORTC soft tissue and bone sarcoma group; Non-Financial Interests, Leadership Role, President: Italian Sarcoma Group. H. Gelderblom: Financial Interests, Institutional, Local PI: Deciphera, Cytovation; Financial Interests, Institutional, Coordinating PI: Boehringer Ingelheim, AmMax Bio, Debiopharm, Abbisko. C.W. Ryan: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, GSK, Pfizer; Financial Interests, Institutional, Local PI: Ayala, Bristol Myers Squib, Daiichi-Sankyo, Deciphera, Exelixis, Genentech, Novartis, Karyopharm, Merck, Nektar, Pfizer, Xynomic, Rain Therapeutics, PTC Therapeutics, NiKang Therapeutics, Shasqi Therapeutics, PF Argentum IP Holdings, LLC. E. Palmerini: Financial Interests, Personal, Advisory Board: SynOx, Daiichi Sankyo, Deciphera Pharmaceuticals; Financial Interests, Personal, Invited Speaker: Peer View Educational. V. Ravi: Financial Interests, Personal, Stocks or ownership: Tracon Pharma, Merck, AstraZeneca, Pfizer, Moderna Therapeutics; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Institutional, Research Funding: Novartis, Tracon Pharma, Aadi, Athenex; Financial Interests, Personal, Other, Travel support: Daiichi Sankyo. R. Saleh: Financial Interests, Personal, Other, Personal fees: Roche. A. Le Cesne: Financial Interests, Personal, Other, Honoraria: Bayer, PharmaMar, Deciphera Pharmaceuticals, LLC. N.M. Bernthal: Financial Interests, Personal, Research Funding: Deciphera Pharmaceuticals, LLC. M. van de Sande: Financial Interests, Personal, Other, Partial travel support: Deciphera Pharmaceuticals, LLC. S. Narasimhan, B. Harrow, A. Saunders: Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Stocks or ownership: Deciphera Pharmaceuticals, LLC. R. Ruiz-Soto: Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Stocks or ownership: Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Royalties: Deciphera Pharmaceuticals, LLC. M.L. Sherman: Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Stocks or ownership: Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Other, Travel support: Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Leadership Role, Deciphera Pharmaceuticals, LLC: Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Royalties: Deciphera Pharmaceuticals, LLC. W.D. Tap: Financial Interests, Personal, Advisory Board: Aadi Biosciences, Abbisko, Amgen, AmMax Bio, Avacta, Bayer, BioAtla, Boehringer Ingelheim, C4 Therapeutics, Cogent Biosciences, Daiichi Sankyo, Foghorn Therapeutics, IMGT, Inhibrx, Ipsen, Lilly, PharmaEssentia, Servier, Sonata, Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Stocks/Shares: Atropos, Certis Oncology Solutions; Financial Interests, Personal, Other, Patent: Companion Diagnostics; Financial Interests, Personal, Other, patent: Enigma; Financial Interests, Institutional, Research Funding: Deciphera Pharmaceuticals, LLC.