LBA78 - Updated efficacy and safety of vimseltinib in patients (pts) with tenosynovial giant cell tumor (TGCT): One-year follow-up from the MOTION phase III trial

Background

Vimseltinib is an investigational, oral, switch-control tyrosine kinase inhibitor specifically designed to selectively and potently inhibit the colony-stimulating factor 1 receptor. In part 1 of the MOTION phase 3 trial (NCT05059262), vimseltinib provided statistically significant and clinically meaningful benefit vs placebo in antitumor activity, active range of motion, and patient-reported outcomes for pts with symptomatic TGCT not amenable to surgery. Here we report the 1-year follow-up after last pt randomization, including the first results from the ongoing part 2.

Methods

MOTION is a 2-part study with double-blind (part 1: 24 weeks) and open-label periods (part 2: up to week 49) followed by an extension period. Pts randomized to placebo in part 1 could cross over to vimseltinib 30 mg twice weekly in part 2. Primary endpoint was objective response rate (ORR) by independent radiological review (IRR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) at week 25. Safety was also evaluated. Duration of response (DOR; by IRR per RECIST v1.1 and tumor volume score [TVS]) was a secondary endpoint. Data cutoff: Feb 22, 2024.

Results

At week 25 (end of part 1), ORR by IRR per RECIST v1.1 and per TVS for pts receiving vimseltinib was 40% and 67%, respectively. For pts with objective responses at week 25, median (range) DOR per RECIST v1.1 and per TVS in part 2 was still not reached (2.5+ to 19.4+ months for both). Of the 83 pts randomized to vimseltinib in part 1, 73 pts continued treatment, and of the 40 pts randomized to placebo, 35 pts crossed over in part 2; overall, a total of 118 pts received vimseltinib. At the time of updated data cutoff, 67% (79/118) of pts were still ongoing. Median (range) treatment duration was 14.4 (1.5 to 25.0) and 8.2 (0.8 to 18.3) months for randomized vimseltinib and crossover vimseltinib groups, respectively. There remains no evidence of cholestatic hepatotoxicity or drug-induced liver injury, and the safety profile was consistent with previously reported data.

Conclusions

In this first report of long-term results (≥1 year) from MOTION, vimseltinib continued to be well tolerated and provided long-term antitumor responses in pts with TGCT not amenable to surgery.

Clinical trial identification

NCT05059262.

Editorial acknowledgement

Medical writing and editorial support were provided by Steven Walker, PhD, of AlphaBioCom, a Red Nucleus company, and was funded by Deciphera Pharmaceuticals, LLC.

Legal entity responsible for the study

Deciphera Pharmaceuticals, LLC.

Funding

Deciphera Pharmaceuticals, LLC.

Disclosure

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; Financial Interests, Personal, Invited Speaker, Lectures: Gentili; Financial Interests, Personal, Advisory Board, Advisory board: Servier; Financial Interests, Institutional, Local PI: Advenchen, Deciphera, Epizyme, Daiichi, GSK, Karyopharm, PharmaMar, SpringWorks, Hutchison MediPharma International Inc, Inhibrix, 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. S. Bauer: Financial Interests, Personal, Advisory Role: Adcendo, Bayer, Boehringer Ingelheim, Cogent Biosciences, Daiichi Sankyo, Lilly, IDRx, Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Other, Honoraria: Blueprint Medicine, Boehringer Ingelheim, Pfizer, PharmaMar, Uptodate, Deciphera Pharmaceuticals, LLC; Financial Interests, Institutional, Research Funding: Adcendo, Blueprint Medicine, Incyte, IDRx; Non-Financial Interests, Personal, Other, Participation on a board: University of Aachen; Non-Financial Interests, Personal, Member of Board of Directors: The Connective Tissue Oncology Society, Deutsche Sarkomstiftung; Financial Interests, Personal, Other, Faculty position: European Society for Medical Oncology. A.J. Wagner: Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Advisory Role: Deciphera Pharmaceuticals, LLC; Financial Interests, Institutional, Research Funding: Daiichi Sankyo, Deciphera Pharmaceuticals, LLC. M. van de Sande: Financial Interests, Personal, Other, Partial travel support: Deciphera Pharmaceuticals, LLC. N.M. Bernthal: Financial Interests, Personal, Research Funding: Deciphera Pharmaceuticals, LLC. A.R. Abdul Razak: Financial Interests, Personal, Advisory Role: Boehringer Ingelheim, Medison; Financial Interests, Institutional, Research Funding: Abbisko, AbbVie, Adaptimmune, Amgen, Bayer, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, GSK, Inhibrx, Iterion Therapeutics, Karyopharm Therapeutics, MedImmune, Medison, Merck, Neoleukin Therapeutics, Pfizer, Rain Therapeutics, Roche/Genentech, Symphogen, 23andMe, Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Advisory Board: Inhibrx. A. Italiano: Financial Interests, Personal, Advisory Board: Bayer, Roche, Philips, Chugai, GSK; Financial Interests, Institutional, Coordinating PI: Bayer, AstraZeneca, Roche, MSD, Ipsen, Merck. A. Le Cesne: Financial Interests, Personal, Other, Honoraria: Bayer, PharmaMar, Deciphera Pharmaceuticals, LLC. C. Tait, A. Saunders, B. Harrow: Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Stocks or ownership: Deciphera Pharmaceuticals, LLC. M.G.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.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. J. 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. 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, Enigma; Financial Interests, Institutional, Research Funding: Deciphera Pharmaceuticals, LLC. All other authors have declared no conflicts of interest.