BioXcel Therapeutics Presents Positive Data From Phase 2 Trial of BXCL701 in Aggressive Forms of Prostate Cancer

BioXcel Therapeutics, Inc. recently announced results from its ongoing Phase 2 trial of BXCL701, the company’s investigational, oral innate immunity activator, in metastatic castration-resistant prostate cancer (mCRPC) patients with either adenocarcinoma or small cell neuroendocrine carcinoma (SCNC) phenotype. Results will be highlighted in two poster presentations at the 2022 ASCO Genitourinary Cancers Symposium on February 17, 2022.

“There are, unfortunately, very few treatment options available for patients with mCRPC, especially those with SCNC, for which there are no approved therapies,” said Rahul Aggarwal, MD, Associate Director for Clinical Sciences, UCSF Helen Diller Family Comprehensive Cancer Center and Associate Professor of Hematology/Oncology, UCSF. “These data demonstrate the potential of BXCL701 plus pembrolizumab to redefine the standard of care for patients with advanced disease. The results were particularly encouraging given that patients were not preselected on the basis of predictors of immune response in prostate cancer.”

KEY SCNC FINDINGS

• In the evaluable patient cohort (n = 15), 5 (33%) patients achieved a composite response at the planned interim analysis.
• In patients with measurable disease (n = 12), RECIST-defined partial response was observed in 4 (33%) patients (3 confirmed responses) and the disease control rate, defined as complete response (CR) + partial response (PR) + stable disease (SD), was 58% (7 patients).
• 3 (17%) patients experienced serious adverse events (AEs) possibly related to BXCL701 or pembrolizumab, and 4 (22%) patients discontinued any drug due to AEs.

KEY ADENOCARCINOMA FINDINGS

• In the evaluable patient cohort (n = 29), 6 (21%) patients achieved a composite response.
• In patients with measurable disease (n = 18), RECIST-defined partial response was observed in 4 (22%) patients (3 confirmed responses) and the disease control rate was 83% (15 patients); all responders experienced a decrease in tumor size from baseline.
• In the 29 patients who had at least 1 post-baseline PSA measurement, the PSA₅₀ was 17% including 5 patients who showed a -100% to -57% PSA decrease.
• From historic data, single agent pembrolizumab showed an objective response rate of 3% to 5%, a disease control rate of 12% and a PSA₅₀ response of 6%.
• 5 (12%) patients experienced serious AEs possibly related to BXCL701 or pembrolizumab, and 2 (5%) patients discontinued any drug due to AEs.
• Results support randomized trial expansion to evaluate BXCL701 monotherapy vs. BXCL701-KEYTRUDA combination therapy.

“We are pleased that BXCL701 in combination with pembrolizumab has shown strong clinical activity in these heavily pre-treated mCRPC patients with both adenocarcinoma or SCNC phenotypes, which are particularly aggressive tumors,” said Vincent J. O’Neill, MD, Senior Vice President and Chief Medical Officer of BioXcel Therapeutics. “We are excited about the broad potential of BXCL701 to extend the activity of checkpoint therapy into cold tumor settings and look forward to initiating the randomized trial extension in patients with adenocarcinoma and continuing patient enrollment in SCNC.”

The Phase 2a trial is an open-label, multicenter study to evaluate the safety and efficacy of BXCL701 in combination with pembrolizumab in men with mCRPC presenting with either adenocarcinoma or SCNC phenotypes. Eligibility criteria include progression as defined by PCWG3 criteria and at least 1 but no more than 2 androgen signaling inhibitors (ASI) and at least 1 prior line of taxane chemotherapy for inclusion in the adenocarcinoma cohort, or at least 1 prior line of chemotherapy for inclusion in the SCNC cohort. 29 evaluable mCRPC patients with adenocarcinoma and 15 evaluable mCRPC patients with SCNC received 0.3 mg of BXCL701 twice daily (BID) on days 1 through 14 of a 21-day cycle (0.2 mg BID the first week of Cycle 1) plus 200 mg of pembrolizumab administered intravenously on day 1 and every subsequent 21 days. The primary endpoint of the trial is composite response rate defined as RECIST 1.1 ± PSA₅₀ ± CTC count conversion. Secondary endpoints include duration of response, progression-free survival, overall survival, and biomarker evaluation as measured by changes in circulating cytokines and correlation of outcome with baseline tumor characteristics.

BXCL701 is an investigational orally administered innate immune activator designed to initiate inflammation in the tumor microenvironment. Approved and experimental immunotherapies often struggle to address cancers that appear “cold” or uninflamed. Therefore, BXCL701 may render “cold” tumors “hot,” making them more detectable by the adaptive immune system and thereby facilitating the development of a strong anti-cancer immune response. BioXcel Therapeutics’ preclinical data supports BXCL701’s synergy with both current checkpoint inhibitor-based therapies and emerging immunotherapies directed to activate T-cells, such as IL-2.

BXCL701 is currently being developed as therapy for metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma and small cell neuroendocrine carcinoma (SCNC) phenotypes (both “cold” tumors) and other advanced solid cancers that are “hot” or have become resistant to checkpoint inhibitors.

BioXcel Therapeutics, Inc. is a clinical-stage biopharmaceutical company utilizing artificial intelligence approaches to develop transformative medicines in neuroscience and immuno-oncology. The company’s drug re-innovation approach leverages existing approved drugs and/or clinically validated product candidates together with big data and proprietary machine learning algorithms to identify new therapeutic indices. BioXcel Therapeutics’ two most advanced clinical development programs are BXCL501, an investigational, proprietary, orally dissolving thin film formulation of dexmedetomidine for the treatment of agitation associated with psychiatric and neurological disorders, and BXCL701, an investigational, orally administered, systemic innate immunity activator in development for the treatment of aggressive forms of prostate cancer and advanced solid tumors that are refractory or treatment naïve to checkpoint inhibitors. For more information, visit www.bioxceltherapeutics.com.