Treatment with BXCL701 (talabostat) in combination with pembrolizumab demonstrated “encouraging” antitumor activity in patients with very late-line, refractory metastatic castration-resistant prostate cancer (mCRPC) with adenocarcinoma phenotype, according to findings presented at the 2022 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium.

BXCL701 is an investigational, first-in-class, oral small molecule inhibitor of dipeptidyl peptidases designed to initiate inflammation in the tumor microenvironment, thus making the tumors more responsive to immunotherapies. In a phase 1b/2 study ( Identifier: NCT03910660), BXCL701 was evaluated in combination with pembrolizumab, a PD-1 inhibitor, in mCRPC patients with adenocarcinoma phenotype as well as in small-cell neuroendocrine carcinoma (SCNC). 

Eligibility criteria included progression as defined by PCWG3 (Prostate Cancer Working Group 3) on 1 or 2 androgen receptor pathway target agents (eg, abiraterone acetate and/or enzalutamide) and at least 1 regimen/line of taxane containing chemotherapy. As of September 27, 2021, 40 adenocarcinoma patients (26 evaluable; 12 in active treatment) were enrolled; all had previously received taxane chemotherapy and 1st and/or 2nd generation androgen deprivation therapy, and had a median of 5 prior lines of treatment. Forty-four percent of patients were reported to have bone only disease.

Continue Reading

Patients received pembrolizumab 200mg intravenously every 21 days plus BXCL701 0.2mg orally twice a day for a week with step-up to 0.3mg twice daily on days 8 to 14, and 0.3mg twice daily on days 1 to 14 for subsequent cycles. The primary endpoint was the composite response rate defined as RECIST 1.1 criteria; circulating tumor cell (CTC) conversion from greater than 5/7.5mL to less than 5/7.5mL per Veridex assay; and 50% or greater prostate-specific antigen (PSA50) decline from baseline.

At a median follow-up of 12 weeks, results showed that the composite response rate was 23% (n=6/26), of which 2 patients had a RECIST-defined confirmed partial response and 1 patient had an unconfirmed partial response. Additionally, the disease control rate was reported to be 63% in 19 patients with measurable disease.

In the 31 patients with at least 1 post baseline PSA measurement, the PSA50 was 16%, including 3 patients who had a PSA decrease of around 90%. In 8 CTC evaluable patients, CTC conversion was found to be 25%. There was a decrease in tumor burden among all responders, including 5 out of 6 responders who were microsatellite stable.

As for safety, treatment with BXCL701 plus pembrolizumab showed acceptable tolerability. There was no evidence of increased immune-related adverse events compared with historic controls with checkpoint inhibitors. Treatment-related adverse events were consistent with cytokine activation including hypotension, edema, fever, and fatigue.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Zhang J, Aggarwal RR, Tagawa ST, et al. BXCL701: First-in-class oral activator of systemic innate immunity combined with pembrolizumab, in patients with metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma phenotype — Phase 2a results. Presented at: ASCO-GU 2022; February 17-19, 2022; Abstract 125.

This article originally appeared on MPR