1769P - Safety and efficacy with vimseltinib in patients (pts) with tenosynovial giant cell tumor (TGCT) who received no prior anti–colony-stimulating factor 1 (CSF1) therapy: Ongoing phase II study

Background

Vimseltinib 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 demonstrated statistically significant and clinically meaningful improvements in the primary and all key secondary endpoints vs placebo. Here, we will report long-term safety and efficacy from cohort A of the phase II part (expansion; enrollment complete) of an ongoing phase I/II study (NCT03069469) for pts with TGCT treated with vimseltinib.

Methods

Pts with symptomatic TGCT not amenable to surgery and no prior anti-CSF1/CSF1R therapy (previous imatinib or nilotinib allowed) received vimseltinib 30 mg twice weekly (recommended phase II dose). The primary objectives were safety, tolerability, and antitumor activity (by independent radiological review [IRR] using Response Evaluation Criteria in Solid Tumors version 1.1); antitumor activity by IRR using tumor volume score was a secondary objective.

Results

In cohort A, 46 pts with TGCT with no prior anti-CSF1/CSF1R therapy were enrolled. At a prior data cutoff (June 2023), most treatment-emergent adverse events (TEAEs) were grade 1/2. Grade 3/4 TEAEs (>5% of pts) were increased creatine phosphokinase and hypertension. There was no evidence of cholestatic hepatotoxicity or drug-induced liver injury. Median treatment duration was 21.0 months (range, 0.2–30.3). Antitumor activity was robust (Table). Updated results will be presented, including long-term safety, duration of response, and best overall response with 8 months of additional follow-up. Table: 1769P

Data shown as n (%). Data cutoff: June 27, 2023; 45 of 46 pts had ≥1 post-baseline imaging assessment at data cutoff (efficacy evaluable). ^aPts that discontinued treatment prior to or reached week 25 were included. ^bOne response occurred prior to week 25 but the patient discontinued the study before week 25 and was considered a nonresponder. BOR, best overall response; RECIST v1.1, Response Evaluation Criteria in Solid Tumors version 1.1; TVS, tumor volume score.

Conclusions

Vimseltinib is well tolerated and demonstrates robust antitumor activity in pts with TGCT. Updated results are expected to support long-term safety and efficacy of vimseltinib in pts with TGCT not amenable to surgery with no prior anti-CSF1/CSF1R therapy.

Clinical trial identification

NCT03069469.

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.

Funding

Deciphera Pharmaceuticals, LLC.

Disclosure

C. Serrano: Financial Interests, Personal, Advisory Board: Deciphera Pharmaceuticals, Blueprint Medicines, Immunicum AB, IDRX, CogentBio, Newbay; Financial Interests, Personal, Invited Speaker: PharmaMar, Roche; Financial Interests, Institutional, Research Grant: IDRX; Financial Interests, Institutional, Steering Committee Member: Deciphera, Newbay; Financial Interests, Institutional, Local PI: IDRX, CogentBio; Non-Financial Interests, Member of Board of Directors: Spanish Group for Sarcoma Research (GEIS), Spanish Society of Medical Oncology (SEOM); Non-Financial Interests, Other, Faculty member: European Society of Medical Oncology (ESMO); Other, Travel Grant: PharmaMar, Pfizer, Bayer AG, Gilead. J. Blay: Financial Interests, Institutional, Invited Speaker: 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. P. Rutkowski: Financial Interests, Personal, Invited Speaker, Honoraria for lectures: MSD, BMS, Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD, BMS, Pierre Fabre, Merck, Sanofi, Blueprint Medicines, Philogen; Financial Interests, Personal, Invited Speaker: Merck, Sanofi, Novartis, AstraZeneca; Financial Interests, Institutional, Research Grant, research grant for ISS: Pfizer; Financial Interests, Institutional, Funding, research grant for institution: BMS; Non-Financial Interests, Member of Board of Directors: Polish Society of Surgical Oncology; Non-Financial Interests, Member of Board of Directors, President: Polish Oncological Society. H. Gelderblom: Financial Interests, Institutional, Local PI: Deciphera, Cytovation; Financial Interests, Institutional, Coordinating PI: Boehringer Ingelheim, AmMax Bio, Debiopharm, Abbisko. 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 Ingelheim; 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. A. Falcon Gonzalez: Financial Interests, Personal, Advisory Board: Seagen, Novartis, Pfizer, Astra Zeneca, Roche, Esteve; Financial Interests, Personal, Invited Speaker: Pfizer, Novartis, Lilly, Grunenthal pharma, Roche, Astra Zeneca, Daiichi Sankyo. J. Desai: Financial Interests, Personal, Invited Speaker: Pierre Fabre, Merck KGaA, novartis; Financial Interests, Personal, Advisory Board: Bayer, Boehringer Ingelheim, Roche/Genentech, Pfizer, Amgen, Pierre Fabre, Beigene, Axelia, Ellipses; Financial Interests, Coordinating PI: Roche/Genentech, Beigene; Financial Interests, Local PI: Amgen, AstraZeneca, GSK, Novartis; Financial Interests, Steering Committee Member: Pfizer; Non-Financial Interests, Principal Investigator: Beigene, Roche/Genentech, Amgen, Pfizer, Novartis, Boehringer, MapCure, SpringWorks, AstraZeneca, Vivace, Incyte; Non-Financial Interests, Member: ASCO, AACR; Non-Financial Interests, Leadership Role: Australia New Zealand Sarcoma Association; Other, Not-for-profit. Director-uncompensated: Cancer Trials Australia. A. Le Cesne: Financial Interests, Personal, Other, Honoraria: Bayer, PharmaMar, Deciphera Pharmaceuticals, LLC. V. Ferraresi: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Novartis; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb, Novartis, Pierre Fabre, MSD Oncology. E. Palmerini: Financial Interests, Personal, Advisory Board: SynOx, Daiichi Sankyo, Deciphera Pharmaceuticals; Financial Interests, Personal, Invited Speaker: Peer View Educational. B.A. Wilky: Financial Interests, Personal, Advisory Board: Adaptimmune, Daiichi Sankyo, Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Invited Speaker: Agenus; Financial Interests, Personal, Advisory Role: SpringWorks. A.J. Wagner: Financial Interests, Personal, Advisory Role: Daiichi Sankyo, Deciphera Pharmaceuticals, LLC; Financial Interests, Institutional, Research Funding: Daiichi Sankyo, 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: Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Stocks or ownership: Deciphera Pharmaceuticals, LLC.: M.G. Sharma: 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. 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, Leadership Role: Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Stocks or ownership: 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 Therapuetics, 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, Engima; Financial Interests, Institutional, Research Funding: Deciphera Pharmaceuticals, LLC.