1622P - A phase II study of the first-in-class oral innate immune activator BXCL701 with pembrolizumab in patients with metastatic castration-resistant prostate cancer (mCRPC): Long-term follow-up

Background

BXCL701 (talabostat), oral small molecule inhibitor of dipeptidyl peptidases—DPP 8/9, DPP4, fibroblast activation protein (FAP)—triggers inflammasome bridging innate and adaptive immunity. We report results of extended follow-up of a phase 2 study of BXCL701 + pembrolizumab in mCRPC patients (pts) without neuroendocrine transformation.

Methods

Pts with histologically confirmed adenocarcinoma + progression by PCWG3 on ≥1 prior line of cytotoxic chemotherapy were enrolled. Treatment: fully outpatient regimen with pembrolizumab (200 mg IV q21 days) + BXCL701 0.2 mg BID days 1-7, with step-up to 0.3 mg BID days 8-14 and days 1-14 of subsequent cycles. Primary endpoint: composite response rate (CRR: confirmed objective response by RECIST 1.1 and/or PSA₅₀ response and/or CTC conversion). Secondary endpoints: duration of response (DoR), radiographic progression-free survival (rPFS), overall survival (OS), predictive biomarker identification.

Results

42 adenocarcinoma pts enrolled, 29 evaluable for CRR. Median lines of prior systemic therapy: 5.5; range 1 – 11 (taxane 100%). CRR: 21% (6 / 29 pts), all responders (except 1) were TMB low and/or MSS. Objective response rate: 22% (4 / 18 evaluable pts; -71% to -99%) + 1 unconfirmed partial response. Median DoR: 18.3 mos; 95% CI (6.5, NR). PSA₅₀ response: 17% (5 / 29 PSA evaluable pts; -57% to -100%). Median OS: 15.6 mos; 95% CI (10.3, NR); 12-mo OS rate: 62.4%; 95% CI (47%, 83%). Median rPFS: 4.1 mos; 95% CI (2.1, 10); 6-mo rPFS rate: 36.5%; 95% CI (22%, 60%). FAP by IHC (n = 10) positively correlated with response. Most common any grade treatment-related adverse events (AEs): fatigue (47%), nausea (31%), vomiting (21%); 4 pts (8%) experienced a Grade ≥3 immune-related AE.

Conclusions

Combination of BXCL701 + pembrolizumab demonstrates encouraging response rates and median survival times in a genomically unselected, late-line mCRPC patient population with limited standard of care treatment options, coupled with an acceptable safety profile. Results appear favorable to those expected with pembrolizumab monotherapy; further evaluation in a randomized trial is warranted.

Clinical trial identification

NCT03910660.

Editorial acknowledgement

Legal entity responsible for the study

BioXcel Therapeutics, Inc.

Funding

BioXcel Therapeutics, Inc.

Disclosure

P. Borderies, R. Deshpande, V. O'Neill: Financial Interests, Institutional, Leadership Role: BioXcel Therapeutics. All other authors have declared no conflicts of interest.