FDA Grants Fast Track Designation to BXCL701 for mCRPC Phenotype

The FDA has granted a fast track designation to the investigational oral innate immune activator BXCL701 in combination with a checkpoint inhibitor for the treatment of patients with metastatic small cell neuroendocrine prostate cancer (SCNC) who experienced progression on chemotherapy and have no evidence of microsatellite instability, according to a news release by BioXcel Therapeutics, the developer of the therapy.¹

“The FDA’s Fast Track designation for the investigation of BXCL701 in SCNC is an important recognition of our most advanced mmune-oncology asset and an acknowledgment of its potential to address the considerable unmet medical need in these patients. At the same time, it further validates the unique AI-based drug re-innovation approach that we used to discover this asset,” said Vimal Mehta, PhD, CEO of BioXcel Therapeutics, in the news release.¹ “BXCL701 has already demonstrated considerable potential in our clinical trials to date, and we plan to further define its development path while exploring strategic options for our OnkosXcel Therapeutics subsidiary.”

The safety and efficacy of BXCL701 in combination with pembrolizumab is currently under investigation in a phase 2 trial (NCT03910660) of patients with metastatic castration-resistant prostate cancer (mCRPC) of both SCNC or adenocarcinoma phenotypes. Interim findings from the trial were reported at the end of 2023, which showed positive overall survival with the combination in patients with both phenotypes.

Overall, the combination of BXCL701 plus pembrolizumab demonstrated a median overall survival of 13.6 months among patients with SCNC. The 12-month survival rate was 56% at 1-year follow-up.²

Further, the combination demonstrated a median overall survival of 15.5 months among patients with the adenocarcinoma phenotype. The 12-month survival rate with BXCL701 plus pembrolizumab in these patients was 59% at 1-year follow-up.³

In total, the phase 2 study enrolled 28 patients with SCNC and 29 patients with the adenocarcinoma phenotype. Patients in both cohorts received 0.3 mg of BXCL701 twice daily on days 1 through 14 of a 21-day cycle (0.2 mg twice daily the first week of cycle 1) plus 200 mg of pembrolizumab administered intravenously on day 1 and every subsequent 21 days.

The primary end point for phase 2a of the study is the composite response rate, defined as either objective response as determined by RECIST 1.1 and/or a prostate-specific antigen decrease of at least 50% and/or circulating tumor cell count conversion. The primary end point for phase 2b of the study is response rate in patients treated with the combination and with BXCL701 monotherapy. The trial’s secondary end points include duration of response, progression-free survival, overall survival, and biomarker evaluation, as measured by changes in circulation cytokines and correlation of outcome with baseline tumor characteristics.

The study is expected to have final results by the end of 2025.⁴

Vincent J. O’Neill, MD, executive vice president, chief of product development and medical officer of BioXcel Therapeutics, concluded in the news release, “SCNC is characterized by poor prognosis and a low survival rate, and current treatment options are suboptimal. We are encouraged by the potential of BXCL701, which has demonstrated clinical proof of concept in both SCNC and adenocarcinoma. Following the positive survival results from our Phase 2 trial that we reported at the end of last year, we look forward to further discussing the registration path at an upcoming meeting with the FDA.”¹

References:

1. BioXcel Therapeutics receives FDA Fast Track Designation for BXCL701 for treatment of small cell neuroendocrine prostate cancer (SCNC). News release. BioXcel Therapeutics. February 12, 2024. Accessed February 13, 2024. https://www.biospace.com/article/releases/bioxcel-therapeutics-receives-fda-fast-track-designation-for-bxcl701-for-treatment-of-small-cell-neuroendocrine-prostate-cancer-scnc-/

2. 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 February 13, 2024. https://ir.bioxceltherapeutics.com/news-releases/news-release-details/bioxcel-therapeutics-reports-positive-overall-survival-results

3. BioXcel Therapeutics reports positive overall survival results from single-arm, open-label phase 2 trial of BXCL701 in patients with metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma phenotype. News release. BioXcel Therapeutics. November 8, 2023. Accessed February 13, 2024. https://ir.bioxceltherapeutics.com/news-releases/news-release-details/bioxcel-therapeutics-reports-positive-overall-survival-results-0

4. A trial of BXCL701 and pembrolizumab in patients with mCRPC either small cell neuroendocrine prostate cancer or adenocarcinoma phenotype. ClinicalTrials.gov. Last updated May 23, 2023. Accessed February 13, 2024. https:// clinicaltrials.gov/ct2/show/NCT03910660