Pembrolizumab plus novel agent shows promising OS in small cell neuroendocrine prostate cancer

The combination of the investigational agent BXCL701 and pembrolizumab (Keytruda) elicited promising overall survival (OS) results in patients with small cell neuroendocrine prostate cancer (SCNC), according to findings from a phase 2 trial.¹

“SCNC represents a major unmet medical need, with the majority of patients unfortunately succumbing to their disease in less than one year following chemotherapy. The results of this trial suggest that BXCL701 has the potential to extend the lives of patients, and I look forward to its continued clinical development,” stated Aggarwal.

In the single-arm, open-label trial, the median OS was 13.6 months (95% CI, 10.9–NR) and the 12-month OS rate was 56.5% in this patient population.

“OS is the most meaningful measure by which the effectiveness of an oncology treatment is evaluated. Though these results are based on a non-randomized cohort of patients, observing a median OS of this duration including patients with long-term survival at 12 months and beyond shows exceptional promise, bearing in mind historic data with checkpoint inhibitor monotherapy in this high-risk subset of prostate cancer,” Principal Investigator Rahul Aggarwal, MD, associate director for clinical sciences, Helen Diller Family Comprehensive Cancer Center, and professor of medicine at the University of California San Francisco (UCSF), stated in a news release.¹

BXCL701 is designed to modulate the tumor microenvironment by activating innate immunity, followed by adaptive immunity, ultimately resulting in cancer cell death.

The trial enrolled patients with histologically confirmed de novo or treatment-emergent SCNC. To be eligible for enrollment, patients needed to have received 1 or more prior lines of systemic therapy, experienced disease progression per Prostate Cancer Clinical Trials Working Group 3 criteria, and an ECOG performance status of 0 to 2. For those with treatment-emergent SCNC, a serum testosterone level of less than 50 ng/dL during screening was required.²

Patients were excluded if they had received more than 2 cytotoxic chemotherapy regimens for mCRPC or had prior treatment with an anti–PD-1, anti–PD-L1, or anti–PD-L2 agent. Prior treatment with another agent directed to another co-inhibitory T-cell receptor was also prohibited.²

Overall, there were 34 patients (median age, 67.5 years) enrolled in the phase 2 study. Sixty-two percent of patients had a visceral metastasis at any site, and 32% had visceral metastases of the liver. The median number of prior lines of systemic therapy received was 3 (range, 1-8).³

At the data cutoff date of September 6, 2023, there were 28 efficacy evaluable patients able to be assessed for OS.

Previously reported data from the trial showed that the objective response rate was 20% among 25 patients who were evaluable for response. Patient responses included 4 confirmed partial responses (PRs) and 1 unconfirmed PR.³

“SCNC represents a major unmet medical need, with the majority of patients unfortunately succumbing to their disease in less than one year following chemotherapy. The results of this trial suggest that BXCL701 has the potential to extend the lives of patients, and I look forward to its continued clinical development,” stated Aggarwal.

Reference

1. BioXcel Therapeutics Reports Positive Overall Survival Results from Single-Arm, Open-Label Phase 2 Trial of BXCL701 in Patients with Small Cell Neuroendocrine Prostate Cancer. Published online and accessed October 10, 2023. https://ir.bioxceltherapeutics.com/news-releases/news-release-details/bioxcel-therapeutics-reports-positive-overall-survival-results

2. CT.gov. A Trial of BXCL701 and Pembrolizumab in Patients With mCRPC Either Small Cell Neuroendocrine Prostate Cancer or Adenocarcinoma Phenotype. Last updated May 23, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT03910660

3. Aggarwal RR, Zhang J, Monk P, 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. J Clin Oncol. 2023;41(suppl 6):176. doi:10.1200/JCO.2023.41.6_suppl.176