BXCL701 Earns FDA FTD in Small Cell Neuroendocrine Prostate Cancer

Investigators previously reported positive findings from a phase 2 trial (NCT03910660) evaluating BXCL701 in combination with pembrolizumab (Keytruda).

The FDA has granted fast track designation to the investigational oral innate immune activator BXCL701 in combination with a checkpoint inhibitor as a treatment for patients with metastatic small cell neuroendocrine prostate cancer (SCNC) that has progressed following prior chemotherapy, according to a press release from BioXcel Therapeutics, Inc.¹

Developers are assessing whether treatment with BXCL701 can turn “cold” tumors “hot” and help the adaptive immune system detect them more easily. Additionally, preclinical data supported the agent’s potential to be combined with checkpoint inhibitors and other types of immunotherapies for T-cell activation.

“The FDA’s fast track designation for the investigation of BXCL701 in SCNC is an important recognition of our most advanced immuno-oncology asset and an acknowledgment of its potential to address the considerable unmet medical need in these patients,” Vimal Mehta, PhD, chief executive officer at BioXcel Therapeutics, said in the press release. “At the same time, it further validates the unique [artificial intelligence]-based drug reinnovation approach that we used to discover this asset. 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.”

Investigators previously reported positive findings from a phase 2 trial (NCT03910660) evaluating BXCL701 in combination with pembrolizumab (Keytruda). In a cohort of 28 evaluable patients with SCNC, the combination produced a median overall survival (OS) of 13.6 months (95% CI, 10.9-not reached [NR]).² Additionally, the OS rate at 12 months was 56.5%.

“SCNC represents a major unmet medical need, with the majority of patients unfortunately [dying] in less than 1 year following chemotherapy,” lead investigator Rahul Aggarwal, MD, associate director for Clinical Sciences at Helen Diller Family Comprehensive Cancer Center and a professor of Medicine at the University of California San Francisco, said in a press release on these data.² “The results of this trial suggest that BXCL701 has the potential to extend the lives of patients, and I look forward to its continued clinical development.”

Results from a cohort of patients with metastatic castration-resistant prostate cancer (CRPC) of the adenocarcinoma were also previously reported.³ Among 29 evaluable patients with adenocarcinoma, BXCL701 plus pembrolizumab elicited a median OS of 15.5 months (95% CI, 9.6-NR). The 12-month OS rate was 59%.

“…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,” Vincent J. O’Neill, MD, chief of Product Development and medical officer at BioXcel Therapeutics, said regarding the adenocarcinoma data.³

In the open-label, multi-center, phase 2 trial, patients received BXCL701 at 0.3 mg twice a day on days 1 to 14 of a 21-day cycle plus pembrolizumab intravenously at 200 mg on day 1 and every subsequent 21 days.

The trial’s primary end point was the composite response rate. Secondary end points included duration of response, progression-free survival, OS, and biomarker evaluation as determined based on changes in circulating cytokines and correlation of outcome with baseline tumor characteristics.

“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,” O’Neill concluded.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, Inc. February 12, 2024. Accessed February 12, 2024. http://tinyurl.com/yc788fas
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 12, 2024. http://tinyurl.com/z88dntm2
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 12, 2024. http://tinyurl.com/yckestyd