Combination talabostat and pembrolizumab has shown antitumor activity in patients who have metastatic castration-resistant prostate cancer (mCRPC) with small-cell neuroendocrine carcinoma (SCNC) phenotype, according to research presented at the 2023 ASCO Genitourinary Cancers Symposium.

Talabostat (BXCL701) is a first-in-class oral innate immune activator that inhibits dipeptidyl peptidase, leading to inflammasome activation, induction of pro-inflammatory cytokines and chemokines, and infiltration of natural killer cells and T cells within the tumor, explained study presenter Rahul Raj Aggarwal, MD, of the Helen Diller Family Comprehensive Cancer Center in San Francisco, California.

Dr Aggarwal presented results from a phase 2a trial ( Identifier: NCT03910660) of talabostat and pembrolizumab in mCRPC patients with de novo SCNC or treatment-emergent SCNC whose disease had progressed on 1 or more prior lines of systemic therapy.

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The analysis included 34 patients. At baseline, their median age was 67.5 (range, 54-80) years, and they had received a median of 3 (range, 1-8) prior lines of systemic therapy.

The patients received talabostat at 0.2 mg twice a day on days 1-7, with step up to 0.3 mg twice a day on days 8-14 in the first cycle. This was followed by talabostat at 0.3 mg twice a day on days 1-14 of subsequent cycles. They received pembrolizumab at 200 mg on day 1 every 3 weeks.

At the data cutoff, 25 patients were evaluable for response. The median follow-up was 30.8 weeks, and the median duration of treatment was 9 weeks.

The objective response rate was 20%, and the disease control rate was 48%. Four patients had a confirmed partial response (PR), 1 had an unconfirmed PR, and 7 had stable disease. The remaining 13 patients had progressive disease.

The median duration of response exceeded 6 months. All responders had microsatellite stable disease and/or low tumor mutational burden, Dr Aggarwal noted.

The safety population included 34 patients. Adverse events (AEs) that were considered at least possibly related to talabostat or pembrolizumab were fatigue (32%), hypotension (21%), pruritus (21%), dizziness (18%), and nausea (12%). There was 1 fatal AE (tumor lysis syndrome), and 1 patient had a grade 3 immune-related AE (colitis).

Based on these results, a phase 2b study is expected to start soon, Dr Aggarwal said.

Disclosures: This research was supported by BioXcel Therapeutics. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Aggarwal RR, Zhang J, Zhu X, et al. First-in-class oral innate immune activator BXCL701 combined with pembrolizumab in patients with metastatic, castration-resistant prostate cancer (mCRPC) of small cell neuroendocrine (SCNC) phenotype: Phase 2a final results. ASCO GU 2023. February 16-18, 2023. Abstract 176.

This article originally appeared on Cancer Therapy Advisor