Pembrolizumab-Based Combo Elicits Treatment Responses in Rare Type of Prostate Cancer

Adding the investigational oral drug BXCL701 to pembrolizumab appears effective in small cell neuroendocrine metastatic castration-resistant prostate cancer, a rare and aggressive disease.

Positive topline findings read out of a phase 2 trial (NCT03910660) assessing BXCL701, an oral innate immune activator, plus pembrolizumab (Keytruda) as a treatment for patients diagnosed with small cell neuroendocrine metastatic castration-resistant prostate cancer (mCRPC), according to a press release from BioXcel.1

In particular, investigators highlighted the combination’s positive response rate in the population. Full data from the study are expected to be presented at the 2023 Genitourinary Cancers Symposium.

“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 at OnkosXcel Therapeutics, a wholly owned subsidiary of BioXcel Therapeutics, said in the press release.

BXCL701 was designed to cause inflammation within the tumor microenvironment. As previously approved immunotherapeutics such as pembrolizumab may not be able to address cold tumors, BXCL701 may offer a solution by making tumors detectable via the adaptive immune system. This allows for the development of a robust, anti-tumor response.

Preclinical data have supported the development of BXCL701 in combination with immune checkpoint inhibitors as a potential option for those diagnosed with aggressive types of prostate cancer and advance solid tumors previously untreated with checkpoint inhibitors.

The study included 28 patients diagnosed with histologically confirmed de novo or treatment-emergent small cell neuroendocrine mCRPC. Patients were also required to have progressive disease by PCWG3 criteria and a minimum of 1 prior line of chemotherapy for advanced or metastatic disease.

The regimen included a 0.3 mg dose of BXCL701 twice daily on days 1 to 14 of every 21-day cycle and 0.2 mg in the first week of cycle 1 in addition to 200 mg of intravenous pembrolizumab on day 1 and every 21 days thereafter.

Primary end points for the trial included composite response rate, defined as RECIST 1.1 and/or prostate-specific antigen50 and/or circulating tumor cell count conversion. Secondary study end points were duration of response, progression-free survival, overall survival, and biomarker evaluation focused on change of circulating cytokines and outcome correlation with baseline tumor characteristics.

The FDA gave BXCL701 orphan drug designation as a treatment for acute myeloid leukemia in September 2019 in addition to pancreatic cancer, stage IIb to IV melanoma, and soft tissue sarcoma.2


  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.
  2. BioXcel Therapeutics receives FDA orphan drug designation for BXCL701 for the treatment of acute myeloid leukemia (AML). News release. BioXcel Therapeutics. September 4, 2019. Accessed January 11, 2023.