BXCL701 Plus Pembrolizumab Generates Positive OS Data in Small Cell Neuroendocrine mCRPC


Treatment with the combination of the investigational oral innate immune activator BXCL701 and pembrolizumab led to a median overall survival of 13.6 months in patients with small cell neuroendocrine carcinoma metastatic castration-resistant prostate cancer.

Rahul Aggarwal, MD

Rahul Aggarwal, MD

Treatment with the combination of the investigational oral innate immune activator BXCL701 and pembrolizumab (Keytruda) led to a median overall survival (OS) of 13.6 months (95% CI, 10.9-not reached) in patients with small cell neuroendocrine carcinoma (SCNC) metastatic castration-resistant prostate cancer (mCRPC), according to data from a phase 2 trial (NCT03910660).1

Additional data showed that evaluable patients (n = 28) experienced a 12-month OS rate of 56.5%.

“OS is the most meaningful measure by which the effectiveness of an oncology treatment is evaluated. Though these results are based on a nonrandomized 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,” Rahul Aggarwal, MD, principal investigator of the phase 2 study, associate director for Clinical Sciences at Helen Diller Family Comprehensive Cancer Center, and a professor of medicine at the University of California San Francisco, stated in a news release.

“SCNC represents a major unmet medical need, with the majority of patients unfortunately succumbing to their disease in less than one year following chemotherapy,” Aggarwal added. “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.”

Previously reported data from the phase 2a portion of the study presented at the 2023 Genitourinary Cancers Symposium showed that 28 evaluable patients achieved a composite response rate, including unconfirmed partial responses (PRs), of 25% (95% CI, 8.3%-41%).2 In evaluable patients (n = 25), the overall response rate per RECIST v1.1 criteria was 20% (95% CI, 6.8%-40.7%), including 4 confirmed PRs and 1 unconfirmed PR. Additionally, 28% of patients had stable disease, and 52% had progressive disease. The disease control rate was 48%.

The combination elicited a composite median duration of response (DOR) of 6+ months (range, 1.3-17.4), and the median DOR per RECIST v1.1 criteria was 6+ months (range, 1.8-9.8). In the 27 patients evaluable for prostate-specific antigen (PSA), 11% (95% CI, 2.4%-29%) had a PSA reduction of at least 50% (PSA50) from baseline. In 4 patients evaluable for circulating tumor cells (CTCs), the CTC response rate was 25% (95% CI, 0.6%-80.6%).

The open-label, multicenter study enrolled patients at least 18 years of age with evidence of progressive mCRPC, as defined by Prostate Cancer Working Group 3 criteria, who experienced disease progression during or following completion of at least 1 prior line of systemic therapy for locally advanced or metastatic disease.3 Patients with de novo small cell prostate cancer were not required to have received prior androgen deprivation therapy.

Patients with SCNC needed to have histologic evidence of SCNC, either via archival tissue or a fresh tumor biopsy during screening, and measurable disease per RECIST v1.1 criteria. At least 1 prior line of cytotoxic chemotherapy was required; however, patients who either refused chemotherapy or were considered unsuitable for chemotherapy may have been eligible following discussion with the trial sponsor.

Patients received 0.3 mg of oral BXCL701 twice per day on days 1 through 14 of each 21-day cycle plus 200 mg of intravenous pembrolizumab on day 1 of each cycle. Notably, BXCL701 was given at 0.2 mg twice per day during the first week of cycle 1.1

Composite response rate, defined as either objective response by RECIST v1.1 criteria, PSA50, and/or CTC count conversion served as the trial’s primary end point. Secondary end points included duration of response, progression-free survival, OS, and biomarker evaluation.

“We believe our trial results are highly encouraging for patients with this disease and have potential implications for our evaluation of BXCL701 for the treatment of other high-grade neuroendocrine tumors, such as small cell lung cancer, where effective therapies are lacking,” Vincent J. O’Neill, MD, chief R&D officer at OnkosXcel Therapeutics, said in a news release. “We intend to discuss these data with the FDA to help determine our next steps with clinical development.”


  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://ir.bioxceltherapeutics.com/news-releases/news-release-details/bioxcel-therapeutics-reports-positive-overall-survival-results
  2. 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. J Clin Oncol. 2023;41(suppl 6):176. doi:10.1200/JCO.2023.41.6_suppl.176
  3. A trial of BXCL701 and pembrolizumab in patients with mCRPC either small cell neuroendocrine prostate cancer or adenocarcinoma phenotype. ClinicalTrials.gov. Updated May 23, 2023. Accessed October 10, 2023. https://clinicaltrials.gov/study/NCT03910660
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