Investigators Announce Expansion to Phase 2 for Trial of BXCL701/Pembrolizumab Combo in Small Cell Neuroendocrine Prostate Cancer


BXCL701 and pembrolizumab may resolve the need for FDA-approved therapies for patients with small cell neuroendocrine prostate cancer, according to investigators.

A phase 1b/2 clinical trial (NCT03910660) assessing the use of oral immune activator BXCL701 plus pembrolizumab (Keytruda) in a heavily pretreated population of patients with metastatic castration-resistant prostate cancer (mCRPC) with de novo or treatment-emergent small cell neuroendocrine carcinoma (SCNC) is set to expand to a phase 2a efficacy analysis, according to a press release from drug developer BioXcel Therapeutics.1

The decision to expand came after the protocol-specified efficacy threshold for cohort expansion of 3 composite responses was met.2 Findings from the phase 1b/2 study were presented at the 2021 European Society of Medical Oncology Congress (ESMO) and indicated that those who received treatment with the experimental combination yielded a composite response rate of 26% and a disease control rate of 63%. Moreover, 5% of patients achieved a confirmed partial response (5%) and 11% had an unconfirmed response.

“There is currently no standard of care for [patients with mCRPC] presenting with the SCNC phenotype,” Vincent J. O’Neill, MD, senior vice president and chief medical officer at BioXcel, said in a press release. “SCNC is a particularly rare and difficult to treat variation of mCRPC. The decision to expand the SCNC cohort builds upon positive interim safety and efficacy data from the adenocarcinoma cohort presented last month at ESMO and moves us into the next stage of the evaluation lifecycle.

He continued, “With three composite responses observed among ten evaluable patients, and what we believe is a manageable side effect profile, we continue to be encouraged by BCXL701’s potential to generate an immune response in ‘cold’ tumor types. We intend to continue recruitment of additional patients for our SCNC cohort, and we look forward to the further evaluation of BXCL701 in this mCRPC patient population, as well as in our adenocarcinoma cohort, which also continues enrollment.”

To be eligible for the open-label, multicenter study, patients were required to have experienced progression via Prostate Cancer Working Group 3 criteria, as well as receive at least 1 previous line of treatment with cytotoxic chemotherapy to be enrolled on the SCNC cohort. Moreover, treatment with 1 to 2 androgen signaling inhibitors and 1 line of taxane chemotherapy was necessary to be included in the adenocarcinoma cohort. Investigators reported a total of 23 response-evaluable patients.

Eligible patients who enrolled on the study with SCNC received 0.3 mg of BXCL701 twice daily on days 1 through 14 throughout the 21-day cycle plus 200 mg of intravenous pembrolizumab on day 1 and every subsequent 21-day cycle.

The study’s secondary end points were duration of response, progression-free survival, and overall survival.

Additional findings from the study indicated that 42% of patients achieved stable disease, 5% had a non–complete response or non–progressive disease, and 37% had progressive disease. Moreover, investigators reported a circulating tumor response rate of 25%.


  1. BioXcel Therapeutics announces expansion of phase 2 Trial of BXCL701 in de novo and treatment-emergent small-cell neuroendocrine prostate cancer. News release. October 18, 2021. Accessed October 21, 2021.
  2. Monk P, Zhang J, Costin D, et al. BXCL701 - 1st-in-class oral activator of systemic innate immunity-combined with pembrolizumab, in men with metastatic castration-resistant prostate cancer (mCRPC): Phase II results. Ann Oncol. 2021;32(suppl 5):S626-S677. doi:10.1016/j.annonc.2021.08.1123
Related Videos
Artificial intelligence programs may help introduce new care strategies that minimize the risk of adverse effects in patients with prostate cancer, according to Wayne G. Brisbane, MD.
An artificial intelligence algorithm appears to create accurate focal treatment margins in patients with prostate cancer, according to Wayne G. Brisbane, MD.
Artificial intelligence may be useful in screening for prostate cancer in patients with elevated prostate specific antigen levels who have undergone MRI, according to Wayne G. Brisbane, MD.
Alicia K. Morgans, MD, MPH, from Dana-Farber Cancer Institute indicates that patients with non-metastatic castration-resistant prostate cancer are able to stay on treatment for long periods of time with darolutamide vs enzalutamide and apalutamide.
Andrew J. Armstrong, MD, MSc, spoke about the recent approval of olaparib plus abiraterone acetate and prednisone in patients with BRCA-mutant metastatic castration-resistant prostate cancer.
Expert on prostate cancer
Expert on prostate cancer
Experts on prostate cancer
Expert on prostate cancer
Expert on prostate cancer
Related Content