BXCL701 Plus Pembrolizumab Generates Promising Responses in Small Cell Neuroendocrine mCRPC


The combination of BXCL701 and pembrolizumab produced encouraging responses in patients with small cell neuroendocrine carcinoma metastatic castration-resistant prostate cancer, according to topline data from a phase 2 trial.

Vincent J. O’Neill, MD

Vincent J. O’Neill, MD

The combination of BXCL701 and pembrolizumab (Keytruda) produced encouraging responses in patients with small cell neuroendocrine carcinoma (SCNC) metastatic castration-resistant prostate cancer (mCRPC), according to topline data from a phase 2 trial (NCT03910660) announced by BioXcel Therapeutics.1

The findings have been submitted to the 2023 Genitourinary Cancers Symposium, and full data will be presented at the meeting in February.

“We are pleased that BXCL701 in combination with pembrolizumab has demonstrated an encouraging response rate in this difficult-to-treat cancer with no currently approved FDA therapies,” Vincent J. O’Neill, MD, chief R&D officer of OnkosXcel Therapeutics, a wholly owned subsidiary of BioXcel Therapeutics, stated in a news release. “BXCL701’s promising profile as an oral innate immune activator with a large safety dataset and novel mechanism of action further supports OnkosXcel’s pipeline and use of BioXcel’s AI platform, and reinforces our confidence in BXCL701’s potential to enable checkpoint inhibitor therapy in traditionally cold cancers.”

Treatment-emergent SCNC is a difficult-to-treat histologic subtype of mCRPC that emerges in approximately 20% of patients with mCRPC. The rates of SCNC are increasing due to more widespread use of androgen blockers. SCNC is highly proliferative and aggressive, and this tumor type does not express androgen receptor or prostate-specific antigen (PSA).2

BXCL701 is an investigational, oral innate immune activator designed to initiate inflammation in the tumor microenvironment. Since immunotherapy agents can struggle to address cancers that appear cold or uninflamed, BXCL701 may render cold tumors hot to make them more detectable by the adaptive immune system, facilitating the development of a strong anticancer immune response.

The open-label, multicenter trial enrolled men with histologically confirmed de novo or treatment-emergent SCNC, progression as defined by PCWG3 criteria, and at least 1 prior line of chemotherapy for locally advanced or metastatic prostate cancer.

Patients were not permitted to have received treatment with more than 2 cytotoxic chemotherapy regimens for CRPC; however, chemotherapy in the hormone-sensitive setting did not apply toward this count if the final dose was more than 6 months before study enrollment.3

Twenty-eight patients with SCNC were administered 0.3 mg of BXCL701 twice daily on days 1 to 14, plus 200 mg of intravenous pembrolizumab on day 1 of each 21-day cycle. Notably, BXCL701 was given at 0.2 mg twice daily during the first week of cycle 1.

The primary end point of the trial was complete response rate defined as RECIST v1.1, PSA50, and/or circulating tumor cell count conversion. Secondary end points included duration of response, progression-free survival, overall survival, and biomarker evaluation measured by changes in circulating cytokines and correlation of outcome with baseline tumor characteristics.


  1. BioXcel Therapeutics announces promising top-line results from phase 2 trial of BXCL701 in aggressive form of rare prostate cancer. News release. BioXcel Therapeutics. January 11, 2023. Accessed January 11, 2023. https://bit.ly/3ipjO2g
  2. Tagawa ST, Zhang J, Monk P, et al. BXCL701: first-in-class oral activator of systemic innate immunity combined with pembrolizumab, in patients with metastatic castration-resistant prostate cancer (mCRPC) of small-cell neuroendocrine carcinoma (SCNC) phenotype—phase 2a interim results. J Clin Oncol. 2022;40(suppl 6):126. doi:10.1200/JCO.2022.40.6_suppl.126
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