Oral immune activator BXCL701 advances in pipeline for neuroendocrine prostate cancer


Investigators have launched the phase 2a efficacy analysis portion of a phase 1b/2 trial exploring the combination of the oral immune activator BXCL701 plus the immune checkpoint inhibitor pembrolizumab (Keytruda) in heavily pretreated patients with metastatic castration-resistant prostate cancer (mCRPC) with de novo or treatment-emergent small cell neuroendocrine carcinoma (SCNC).1

The decision, which was reported in press release from BXCL701 developer BioXcel Therapeutics, came after the protocol-specified efficacy threshold for cohort expansion of 3 composite responses was met.2 Findings from the phase 1b/2 study (NCT03910660) 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. Published online October 18, 2021. Accessed November 1, 2021. https://bit.ly/3G8BR3s.

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

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