BXCL701 Combo May Improve OS in Small Cell Neuroendocrine Prostate Cancer

"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," according to Rahul Aggarwal, MD.

Investigators of a phase 2 study (NCT03910660) reported positive overall survival (OS) findings in a small population of patients with small cell neuroendocrine prostate cancer who were treated with BXCL701 and pembrolizumab (Keytruda), according to a press release from BioXcel Therapeutics.¹

In an evaluable population of 28 patients, the median OS was 13.6 months (95% CI, 10.9–not reached) at the data cut-off of September 6, 2023. Additionally, the 12-month OS rate was 56.5%. These findings compare favorably with previous reports of single-agent avelumab (Bavencio) in those with aggressive-variant or progressive neuroendocrine prostate cancer, which garnered a median OS of 7.4 months (85% CI, 2.8-12.6).² It was noted, however, that no head-to-head comparison between the 2 agents has been studied.

“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 at Helen Diller Family Comprehensive Cancer Center, and professor of Medicine at the University of California, San Francisco (UCSF), said in the press release.¹

“[Small cell neuroendocrine prostate cancer] represents a major unmet medical need, with the majority of patients unfortunately [dying] in less than 1 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.”

Investigators behind the open-label, multicenter phase 2 study examined the effectiveness of combination BXCL701/pembrolizumab in a population of 28 patients diagnosed with small cell neuroendocrine prostate cancer. The cohort of patients was treated with 0.3 mg of BXCL701 twice a day on days 1 to 14 of every 21-day cycle, including a 0.2 mg dose during the first week of cycle 1. This was coupled with 200 mg of intravenous pembrolizumab on day 1 and every subsequent 21 days.

The study’s primary end point is complete response rate, with secondary end points including progression-free survival, overall survival, and safety.

To be included in the trial, patients needed to have metastatic castration-resistant prostate cancer, with progression occurring after a minimum of 1 previous line of systemic therapy for locally advanced or metastatic disease. Those in the small cell neuroendocrine prostate cancer cohort needed to have previously been treated with at least 1 previous line of cytotoxic chemotherapy or be ineligible for treatment with chemotherapy. Additionally, the population needed to be willing to undergo metastatic tumor biopsy.

A previous readout of the study highlighted durable responses in patients treated with BXCL701/pembrolizumab.3 The combination yielded a composite response rate of 25% and a RECIST response rate of 20%.

References

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. News release. BioXcel Therapeutics. October 10, 2023. Accessed October 10, 2023. https://bit.ly/3F9wTEi
2. Brown LC, Halabi S, Somarelli JA, et al. A phase 2 trial of avelumab in men with aggressive-variant or neuroendocrine prostate cancer. Pro Can Pro Dis. 2022;25:762-769. doi:10.1038/s41391-022-00524-7
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