Oral BXCL701 in combination with pembrolizumab demonstrated anti-tumor activity with durable responses among patients with refractory metastatic castration-resistant prostate cancer of small cell neuroendocrine (SCNC) phenotype.

Rahul Raj Aggarwal, MD, Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, presented final results from the phase 2a study on Thursday, February 16, 2023, at the 2023 ASCO Genitourinary Cancers Symposium in San Francisco, CA.

BXCL701 (talabostat) is an oral, first-in-class small molecule inhibitor of dipeptidyl peptidases. SCNC is an aggressive, proliferative cancer which exhibits limited duration of response to platinum-based chemotherapy. There is currently no standard of care for patients with this phenotype of metastatic castration-resistant prostate cancer in laterlines of therapy.

As of October 11, 2022, there were 27 patients evaluable of the 32 accrued (treatment emergent SCNC, n = 16; de novo SCNC, n = 11). There were19 patients who had previously received platinum chemotherapy. In this study design, there were 15 evaluable patients in stage 1 and 13 in stage 2. Patients received 200 mg pembrolizumab three times a week, plus 0.2 mg of BXCL701 twice daily on days 1 through 7 of cycle 1, with step-up protocol to 0.3 mg twice daily on days 8 through 14, and 0.3 mg twice daily on days 1 through 14 on subsequent cycles. The primary end point of the study was composite response.

As previously reported, with 15 evaluable patients, there were 5 composite responses. The median duration of response was 39 weeks. All responders are microsatellite stable, and or have a low tumor mutational burden. Of the 5 responders, 2 are still actively receiving treatment, with a median duration of follow-up of 48.3 weeks. At the time of abstract submission, there are 9 patients still actively on treatment with the study enrollment ongoing.

This treatment regimen demonstrates acceptable tolerability with no reports of increased immune-related adverse events, as compared to historic controls with checkpoint inhibitors. There were adverse events consistent with cytokine activation—such as hypotension, fever, and fatigue—reported.

Dr Aggarwal and coauthors concluded, “Oral BXCL701 in combination with pembrolizumab demonstrates encouraging anti-tumor activity with durability of response in late-line, refractory metastatic castration-resistant prostate cancer SCNC for which there is currently no standard of care,” adding that the twice daily dosing of BXCL701 “continues to demonstrate an acceptable safety profile.”

Source:

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. Presented at 2023 ASCO Genitourinary Cancers Symposium; February 17-19; San Francisco, CA. Abstract 15