The following article features coverage from the ASCO Genitourinary Cancers Symposium 2022. Click here to read more of MPR‘s conference coverage.

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.

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.