Abstract 1821P
Background
Diffuse TGCT is a rare, locally aggressive neoplasm, where overexpression of colony-stimulating factor 1 (CSF1) drives recruitment of macrophages leading to local inflammation and joint destruction. Vimseltinib (DCC-3014) is an oral, highly selective, switch-control kinase inhibitor of CSF1 receptor (CSF1R). We report the safety and efficacy of patients (pts) with TGCT in the phase 1 arm of the phase 1/2 study (NCT03069469).
Methods
In phase 1 (dose-escalation) and phase 2 (expansion) study, pts with unresectable TGCT were treated with vimseltinib. Primary objectives of phase 1 were to determine the safety, tolerability, and recommended phase 2 dose (RP2D). Antitumor activity was assessed using RECIST version 1.1.
Results
As of Feb 26, 2021, 32 TGCT pts were enrolled in phase 1 and 24 pts remain on study. Median age was 51 years (range, 23–73), median treatment duration was 6.8 months (range, 1–19), and most common disease site was knee in 20 (63%) pts. Treatment-emergent adverse events (AEs) of grade 3–4 in >5% were increases in blood creatine phosphokinase, aspartate aminotransferase (AST), lipase, amylase, and hypertension. Enzyme elevations were consistent with the mechanism of action of CSF1R inhibitors. Treatment-related grade 3 serious AEs in 2 pts: metabolic encephalopathy and vaginal hemorrhage. Dose-limiting toxicity of asymptomatic grade 3 AST increase in 2 pts (1 each in cohorts 5 and 8), both pts had grade 1 AST increase at baseline. Objective responses were observed in 13 (1 complete and 12 partial responses; 45%) of 29 efficacy-evaluable phase 1 pts across all dose cohorts (Table). Enrollment is ongoing in phase 2; all 16 TGCT pts enrolled to date remain on study. Table: 1821P
| Phase 1 TGCT dose cohorts | |||
| Cohort 5 (n = 8) | Cohort 8 (n = 12) | Cohort 9 (n = 9) | |
| Loading dose | 30 mg QD × 5 | 30 mg QD × 3 | 20 mg QD × 3 |
| Dose | 30 mg twice weekly | 10 mg QD | 6 mg QD |
| Objective response rate, n (%) | 4 (50) | 6 (50) | 3 (33) |
| Median duration on study, months | 6.3 | 8.3 | 4.5 |
| QD, once daily. |
Conclusions
Vimseltinib was well tolerated with encouraging and durable antitumor activity across all phase 1 TGCT dose cohorts. Safety profile of vimseltinib remains manageable with longer-term follow-up. Phase 2 safety and preliminary efficacy data at RP2D (30 mg twice weekly) will be presented.
Clinical trial identification
NCT03069469.
Editorial acknowledgement
Medical writing was provided by Uma Chandrasekaran, PhD (Deciphera Pharmaceuticals, LLC); editorial support was provided by Ashfield MedComms and was funded by Deciphera Pharmaceuticals, LLC.
Legal entity responsible for the study
Deciphera Pharmaceuticals, LLC.
Funding
Deciphera Pharmaceuticals, LLC.
Disclosure
P. Rutkowski: Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme Corp.; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Invited Speaker: Pierre Fabre; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Sanofi; Financial Interests, Personal, Invited Speaker: Blueprint Medicines. B. Wilky: Financial Interests, Personal, Other: GlaxoSmithKline; Financial Interests, Personal, Other: Lilly; Financial Interests, Personal, Other: Adaptimmune Therapeutics; Financial Interests, Personal, Other: Advenchen Laboratories; Financial Interests, Personal, Other: Daiichi Sankyo; Financial Interests, Personal, Other: Deciphera Pharmaceuticals; Financial Interests, Personal, Other: Agenus; Financial Interests, Personal, Other: Novartis; Financial Interests, Personal, Advisory Role: Deciphera Pharmaceuticals; Financial Interests, Personal, Advisory Role: Adaptimmune Therapeutics; Financial Interests, Personal, Advisory Role: SpringWorks Therapeutics; Financial Interests, Personal, Advisory Role: Immune Design; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Institutional, Principal Investigator: Merck Sharp & Dohme; Financial Interests, Institutional, Principal Investigator: Agenus. A. Wagner: Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: Deciphera Pharmaceuticals; Financial Interests, Personal, Advisory Role: Epizyme; Financial Interests, Personal, Advisory Role: Mundipharma; Financial Interests, Institutional, Principal Investigator: Aadi Bioscience; Financial Interests, Institutional, Principal Investigator: Daiichi Sankyo; Financial Interests, Institutional, Principal Investigator: Deciphera Pharmaceuticals; Financial Interests, Institutional, Principal Investigator: Eli Lilly; Financial Interests, Institutional, Principal Investigator: Foghorn Therapeutics; Financial Interests, Institutional, Principal Investigator: Karyopharm Therapeutics; Financial Interests, Institutional, Principal Investigator: Plexxikon. M. van de Sande: Financial Interests, Institutional, Research Grant: Daiichi Sankyo; Financial Interests, Institutional, Research Grant: Carbofix Orthopedics; Financial Interests, Institutional, Research Grant: Implantcast. M. Michenzie: 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: Deciphera Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Deciphera Pharmaceuticals. M. Sharma: Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Deciphera Pharmaceuticals. M.L. Sherman: Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Deciphera Pharmaceuticals; Financial Interests, Personal, Other: Pieris Pharmaceuticals. R. Ruiz-Soto: Financial Interests, Personal, Full or part-time Employment: Deciphera Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Deciphera Pharmaceuticals. W. Tap: Financial Interests, Personal, Ownership Interest: Atropos Therapeutics; Financial Interests, Personal, Stocks/Shares: Certis Oncology Solutions; Financial Interests, Personal, Stocks/Shares: Atropos Therapeutics; Financial Interests, Personal, Advisory Board: Innova Therapeutics; Financial Interests, Personal, Advisory Board: Certis Oncology Solutions; Financial Interests, Personal, Other: Eli Lilly; Financial Interests, Personal, Other: EMD Serono; Financial Interests, Personal, Other: Mundipharma; Financial Interests, Personal, Other: C4 Therapeutics; Financial Interests, Personal, Other: Daiichi Sankyo; Financial Interests, Personal, Other: Blueprint Medicines; Financial Interests, Personal, Other: GlaxoSmithKline; Financial Interests, Personal, Other: Agios Pharmaceuticals; Financial Interests, Personal, Other: NanoCarrier; Financial Interests, Personal, Other: Deciphera Pharmaceuticals; Financial Interests, Personal, Other: Adcendo; Financial Interests, Personal, Other: Ayala Pharmaceuticals; Financial Interests, Personal, Other: Kowa; Financial Interests, Personal, Other: Servier Pharmaceuticals; Financial Interests, Personal, Other: AbMax Biotechnology; Financial Interests, Personal, Proprietary Information: Companion Diagnostic. All other authors have declared no conflicts of interest.