BXCL701/Pembrolizumab Combo Prolongs OS in mCRPC of Adenocarcinoma Phenotype

Treatment with the oral innate immune activator BXCL701 combined with pembrolizumab (Keytruda) demonstrated prolonged overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma phenotype, according to results of a phase 2 trial (NCT03910660).¹ The findings were announced in a news release by OnkosXcel, a wholly owned subsidiary of BioXcel Therapeutics, the developer of BXCL701.

The median OS with the combination at the September 6, 2023 data cutoff was 15.5 months (95% CI, 9.6-not reached [NR]), and the 1-year OS rate was 59%.

“Patients with mCRPC who have failed androgen deprivation and taxane-based chemotherapy have few remaining treatment options and, unfortunately, Keytruda to date has not shown additional benefit in this setting,” Vincent J. O’Neill, MD, chief R&D officer, OnkosXcel Therapeutics, stated in the news release. 

“Therefore, we are highly encouraged by these combination data bearing in mind historical data with checkpoint inhibitor monotherapy. In addition, we now have a second positive dataset in a separate cold tumor histology, further increasing our belief that BXCL701 has the potential to inflame the tumor microenvironment of cold tumors, thereby sensitizing them to checkpoint inhibition. We believe the data warrant further evaluation of BXCL701 in this setting and look forward to determining the development path for this program following our end of phase 2 meeting with the FDA scheduled for December.”

There are expected to be an estimated 288,300 new patients with prostate cancer in 2023. Of these patients, 20% of patients are expected to advance to mCRPC; an estimated 80% of mCRPC cases are of the adenocarcinoma phenotype, equating to about 46,128 patients.

In the open-label, multicenter, phase 2 trial, investigators sought to evaluate the efficacy and safety of BXCL701 in combination with pembrolizumab in men with mCRPC of adenocarcinoma phenotype as well as in men with small cell neuroendocrine carcinoma (SCNC). A total of 29 evaluable patients with mCRPC of adenocarcinoma received 0.3 mg of BXCL701 twice daily on days 1 through 14 of a 21-day cycle, with 0.2 mg twice daily the first week of cycle 1, plus 200 mg of intravenous pembrolizumab on day 1 and every subsequent 21 days.

The primary end point was a composite response rate, which is defined as either objective response by RECIST v1.1 criteria and/or prostate-specific antigen 50 and/or a circulating tumor cell count conversion. Secondary end points were duration of response (DOR), progression-free survival, OS, and biomarker evaluation, the latter of which was measured by circulating cytokines changes and correlation of outcome with baseline tumor characteristics.

An update on response rate findings from the phase 2 adenocarcinoma cohort was presented at the 2023 Prostate Cancer Foundation Annual Scientific Retreat. Here, data showed a RECIST v1.1 partial response rate of 28% and the median DOR was 19 months. When compared with the KEYNOTE-199 trial (NCT02787005), which evaluated single-agent pembrolizumab in this refractory mCRPC population, the response rate was 5% and the median DOR was 16.8 months.

In October 2023, the company also announced that OS was prolonged in the SCNC subset, with a median OS of 13.6 months (95% CI, 10.9-NR).²

Previously, the FDA granted orphan drug designations to BXCL701 in acute myelogenous leukemia, pancreatic cancer, stage IIb to IV melanoma, and soft tissue sarcoma.

References

1. 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. BioXcel Therapeutics, Inc. News release. November 8, 2023. Accessed November 8, 2023. https://www.globenewswire.com/news-release/2023/11/08/2776064/0/en/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-.html
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 October 10, 2023. https://ir.bioxceltherapeutics.com/news-releases/news-release-details/bioxcel-therapeutics-reports-positive-overall-survival-results