Abstract 610P
Background
BXCL701 (talabostat), an oral small molecule inhibitor of dipeptidyl peptidases—primarily DPP8/9—triggers the inflammasome to alert and prime immune cells, leading to induction of IL-18 and IL-1ß, bridging innate and adaptive immunity. BXCL701 is evaluated in a phase 1b/2 study in combination with pembrolizumab, in mCRPC patients with adenocarcinoma, and in small-cell neuroendocrine histology patients. Previously completed phase 1b study demonstrated acceptable tolerability and encouraging anti-tumor activity with an objective partial response in an adenocarcinoma patient (MS-stable), and a separate patient with PSA70 response.
Methods
Phase 2 adenocarcinoma patients were required to have progression by PCWG3 on ≥1 androgen signaling inhibitor and ≤2 prior lines of chemotherapy. Patients received pembrolizumab (200 mg IV q21-days) + BXCL701 0.2 mg BID prime with step-up to 0.3 mg BID on days 1-14. Primary endpoint is composite response (RECIST 1.1, PSA50, and/or CTC conversion). Study uses a Simon 2-stage minimax design with 15 evaluable patients in stage 1 and 13 in stage 2. Baseline markers and changes in relevant immune effector cells also evaluated.
Results
As of 4/15/21, 30 adenocarcinoma patients were enrolled: all had prior chemotherapy and a median of 6 prior lines of therapy, 93% previously received abiraterone and/or enzalutamide; 40% have bone-only disease. Median follow-up duration is 9 weeks (range 1-30) / 2.9+ cycles. Although follow-up was short, anti-tumor activity was seen: 27% patients with measurable PSA at baseline achieved any PSA decline, with 2 patients who had a PSA reduction >70%; 2 RECIST 1.1 evaluable patients had a reduction in target lesions, i.e., -50.4% (Partial Response) and -28%. Majority of AEs are consistent with cytokine activation (hypotension, oedema, fever, fatigue).
Conclusions
Oral BXCL701 in combination with pembrolizumab demonstrates encouraging anti-tumor activity in very late-line, refractory mCRPC adenocarcinoma. BXCL701 BID dosing continues to demonstrate an acceptable safety profile. Final study results including early biomarker analyses will be presented.
Clinical trial identification
NCT03910660.
Editorial acknowledgement
Acknowledgements: All patients, their families, and caregivers who make this study possible; participating investigators and their staff; Valery Chatikhine, MD of IQVIA Biotech and IQVIA Biotech team for assisting in the conduct of the study.
Legal entity responsible for the study
BioXcel Therapeutics, Inc.
Funding
BioXcel Therapeutics, Inc.
Disclosure
P. Borderies: Financial Interests, Personal, Stocks/Shares: BioXcel Therapeutics. V. O'Neill: Financial Interests, Personal, Stocks/Shares: BioXcel Therapeutics. All other authors have declared no conflicts of interest.