Abstract 475P
Background
TGCT is a rare, locally aggressive neoplasm caused by upregulation of the colony-stimulating factor 1 (CSF1) gene, resulting in aberrant CSF1 expression and the recruitment of CSF1 receptor (CSF1R)-dependent inflammatory macrophages. Vimseltinib is an oral switch-control tyrosine kinase inhibitor specifically designed to selectively and potently inhibit CSF1R. We report long-term safety and efficacy for patients (pts) with TGCT from the phase I arm (dose escalation) of the phase I/II study.
Methods
Pts with TGCT not amenable to surgery were treated with vimseltinib. The primary objectives were to determine safety, tolerability, and the recommended phase II dose (RP2D).
Results
As of Feb 18, 2022, 32 pts were enrolled (Table); 20 pts remain on study. Overall, only 3 pts discontinued treatment due to an adverse event (AE) or progressive disease. The median treatment duration was 16.4 months. Median age was 51 years (range: 23–73) and the most common location was the knee (63%). Long-term safety was consistent with previous data. Grade 3/4 treatment-emergent AEs in >5% of pts included increases in creatine phosphokinase (CPK), aspartate aminotransferase, lipase, amylase, and hypertension. Enzyme elevations were asymptomatic and consistent with the known class effect of CSF1R inhibitors; no postbaseline bilirubin elevations were observed. There were no new treatment-related serious AEs since the June 7, 2021 data cut. The combined objective response rate (ORR) was 69% (Table); most responses were achieved within 6 months after initiation of treatment. The RP2D is 30 mg twice weekly (no loading dose). Table: 475P
| TGCT dose cohorts | ||||
| Cohort 5 n = 8a | Cohort 8 n = 12 | Cohort 9 n = 12 | Total N = 32 | |
| Loading dose | 30 mg QD x 5 days | 30 mg QD x 3 days | 20 mg QD x 3 days | |
| Dose | 30 mg twice weekly | 10 mg QD | 6 mg QD | |
| Best overall response, n (%) b | ||||
| Complete response | 1 (13) | 0 | 0 | 1 (3) |
| Partial response | 5 (63) | 9 (75) | 7 (58) | 21 (66) |
| Stable disease | 2 (25) | 3 (25) | 5 (42) | 10 (31) |
| Objective response rate, n (%) | 6 (75) | 9 (75) | 7 (58) | 22 (69) |
Percentages are rounded and may not equal the whole. a1 patient does not have central read data and was included as a stable disease assessment. bAssessed using RECIST v1.1 by independent radiologic review; includes all available follow-ups.
Conclusions
Vimseltinib demonstrated long-term tolerability in pts with TGCT not amenable to surgery; no new safety signals were identified. The ORR continues to improve; sustained responses were observed across all dose cohorts both within and after 6 months, demonstrating continued benefit with prolonged treatment.
Clinical trial identification
NCT03069469.
Editorial acknowledgement
Medical writing and editorial support was provided by Lauren Hanlon, PhD, of AlphaBioCom, LLC (King of Prussia, PA, USA) and was funded by Deciphera Pharmaceuticals, LLC (Waltham, MA, USA).
Legal entity responsible for the study
Deciphera Pharmaceuticals, LLC.
Funding
Deciphera Pharmaceuticals, LLC.
Disclosure
H. Gelderblom: Financial Interests, Institutional, Invited Speaker: Daiichi, Deciphera, Novartis, Boehringer Ingelheim, AmMax Bio, Debiopharm, Cytovation. A. Abdul Razak: Financial Interests, Personal, Advisory Role: Merck, Adaptimmune, Bayer, Inhibrx, Medison; Financial Interests, Institutional, Funding: Deciphera, Karyopharm Therapeutics, Pfizer, Roche/Genentech, Bristol Myers Squibb, MedImmune, Amgen, GSK, Blueprint Medicines, Merck, AbbVie, Adaptimmune, Iterion Therapeutics, Neolukin. J. Martin-Broto: Financial Interests, Personal, Expert Testimony, Honoraria: Lilly, PharmaMar, Eisai, Bayer; Financial Interests, Personal, Invited Speaker: PharmaMar; Financial Interests, Personal, Advisory Board, Speaker: Tecnofarma, Asofarma; Financial Interests, Institutional, Invited Speaker: PharmaMar, Eisai, Novartis, IMMIX Biopharma, Lixte, Karyopharm, Bayer, Celgene, Pfizer, BMS, Blueprint, Deciphera, NEKTAR, FORMA, Amgen, Daiichi Sankyo, Lilly, AROG, Adaptimmune, GSK. B.A. Wilky: Financial Interests, Personal, Other, consulting for curriculum development: Springworks; Financial Interests, Personal, Advisory Board: Deciphera, Adaptimmune, Daiichi Sankyo; Financial Interests, Institutional, Invited Speaker: Agenus. 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; Financial Interests, Institutional, Research Grant, research grant for ISS: Pfzer; Financial Interests, Institutional, Funding, research grant for institution: BMS; Non-Financial Interests, Invited Speaker: Polish Society of Surgical Oncology; Non-Financial Interests, Officer: ASCO; Non-Financial Interests, Invited Speaker, President Elect: Polish Oncological Society. S. Narasimhan: Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Deciphera Pharmaceuticals. M. Vallee: Financial Interests, Personal, Full or part-time Employment, I am an employee of Deciphera Pharmaceuticals: Deciphera Pharmaceuticals; Financial Interests, Personal, Stocks/Shares, I own Deciphera Pharmaceuticals stock: Deciphera Pharmaceuticals. M. Sharma: Financial Interests, Institutional, Full or part-time Employment, Senior Medical Director, Clinical Development: Deciphera Pharmaceuticals; Financial Interests, Institutional, Stocks/Shares: Deciphera Pharmaceuticals. R. Ruiz-Soto: Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals, LLC; Financial Interests, Personal, Stocks/Shares: Deciphera Pharmaceuticals, LLC, ImmunoGen; Financial Interests, Personal, Other, I am an inventor in 3 patents with ImmunoGen, I transferred the rights to ImmunoGen. I have not received (and I will not receive) any royalties: ImmunoGen; Financial Interests, Personal, Other, I am an inventor in pending patents at Deciphera. I have transferred the rights to Deciphera, I have not received (and will not receive) any royalties: Deciphera. M.L. Sherman: Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals; Financial Interests, Personal, Invited Speaker: Pieris Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Deciphera Pharmaceuticals, Pieris Pharmaceuticals. W.D. Tap: Financial Interests, Personal, Advisory Board: Eli Lilly, Daiichi Sankyo, Nano Carrier, Blueprint, Deciphera, C4 Therapeutics, Foghorn Therapeutics, AmMaxBio, MundiBioPharma, Novo Holdings, Servier, Medpacto, Ayala Pharmaceuticals, Kowa Research Institute, Epizyme Inc (Nexus Global Group), Bayer, Cogent Biosciences, Amgen, Aadi Biosciences; Financial Interests, Personal, Invited Speaker: EMD Serono, PER; Financial Interests, Personal, Stocks/Shares: Certis Oncology Solutions, Atropos; Financial Interests, Personal, Other, *patent: - Companion Diagnostics for CDK4 inhibitors (14/854,329); Financial Interests, Institutional, Funding: Novartis, Eli Lilly, Plexxxicon, Daiichi Sankyo, Tracon Pharma, Blueprint Medicines, Immune Design, BioAlta, Deciphera.