Prostate Cancer Coverage from Every Angle

Novel Immunotherapy Combination in Metastatic Prostate Cancer Moves on to Phase II

By: Celeste L. Dixon
Posted: Wednesday, January 13, 2021

Trials of the agent BXCL701 (talabostat) continue in metastatic castration-resistant prostate cancer after its recommended phase II dose was determined in a phase Ib study. Rahul Aggarwal, MD, of the University of California, San Francisco, and colleagues described their work with talabostat—an oral small molecule inhibitor of dipeptidyl peptidases—during the 2020 Society for Immunotherapy of Cancer (SITC) Annual Meeting (Abstract 341) and simultaneously in the Journal for ImmunoTherapy of Cancer.

A total of 13 patients with progressing metastatic castration-resistant prostate cancer participated. Although these observations are preliminary, talabostat exhibited antitumor activity in one and three patients who achieved a prostate-specific antigen response and stable disease, respectively. In addition, the drug was quantifiable in plasma, reported the team.

The phase II dose was determined to be 0.6 mg/day. The investigators found that splitting the targeted drug delivery was associated with better tolerability and no reported dose-limiting toxicities. According to Dr. Aggarwal and co-investigators, splitting the dose resulted in lower hypotension and peripheral edema rates.

Talabostat, the researchers described, “triggers inflammasome-mediated pyroptosis in macrophages leading to induction of IL-18 and IL-1beta, bridging between innate and adaptive immunity.” They noted that single-agent talabostat had resulted in objective responses in patients with stage IV melanoma in a prior unpublished clinical study. In their trial, they administered talabostat in conjunction with pembrolizumab, and that will continue in the currently enrolling phase II trial.

Disclosure: For full disclosures of the study authors, visit

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