BXCL701 Gains Fast Track Designation for mCRPC Treatment

• BXCL701, an investigational oral innate immune activator, is being evaluated in combination with pembrolizumab (Keytruda) in patients with metastatic castration-resistant prostate cancer (mCRPC) of both small cell neuroendocrine (SCNC) and adenocarcinoma phenotypes.

• Initial findings from the phase 2 trial showed that among patients with SCNC, the median overall survival (OS) was 13.6 months, with a 12-month OS rate of 56.5%. For patients with the adenocarcinoma phenotype, the median OS was 15.5 months, with a 12-month OS rate of 59%.

• This designation recognizes the potential of BXCL701 to address the unmet medical need in these patients.

The FDA has granted a fast track designation to the combination of BXCL701 with an immune checkpoint inhibitor (CPI) for the treatment of patients with metastatic SCNC prostate cancer with progression on chemotherapy and no evidence of microsatellite instability, according to BioXcel Therapeutics, Inc.¹

BXCL701 is an investigational, oral innate immune activator made to inflame the tumor microenvironment and augment CPI activity. A phase 2 trial (NCT03910660) is currently ongoing evaluating BXCL701 in combination with pembrolizumab (Keytruda) in patients with mCRPC with SCNC and adenocarcinoma phenotypes.

Findings showed that among the 28 patients in the SCNC cohort, (95% CI, 10.9-not reached [NR]), and the 12-month OS rate was 56.5%.² At the most recent data cutoff of September 6, 2023, the combination demonstrated a median OS of 15.5 months (95% CI, 9.6-NR) among the 29 patients in the adenocarcinoma cohort, and the OS rate at 12 months was 59%.³

“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. At the same time, it further validates the unique AI-based drug reinnovation approach that we used to discover this asset,” said Vimal Mehta, PhD, chief executive officer of BioXcel Therapeutics, in a press 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.”

In the open-label, single-arm, multicenter phase 2 trial, the safety and efficacy of BXCL701 plus pembrolizumab is being evaluated for the treatment of mCRPC of the adenocarcinoma or SCNC phenotype.² Patients with SCNC were given BXCL701 twice a day at a dose of 0.2 mg on days 1 through 7, 0.3 mg on days 7 through 14 for the first 21-day cycle, and 0.3 mg after, in addition to pembrolizumab given via intravenous infusion at a dose of 200 mg on day 1 of each cycle.

PC-3 human prostate cancer cells: © heitipaves - stock.adobe.com

Enrollment is open to patients with evidence of progressive metastatic castration-resistant disease, as defined by Prostate Cancer Working Group 3 criteria, and documented progression during or following the completion of at least 1 previous line of systemic therapy for locally advanced or metastatic disease.⁴ Patients must have adequate baseline hematologic function, adequate baseline organ function, resolved from their acute toxic effects of previous anticancer therapy to ≤ grade 1, with the exception of grade 2 to 3 peripheral neuropathy or any grade of alopecia, and have an ECOG performance status of 0 to 2.

Further, patients with de novo small cell prostate cancer were not required to have received prior androgen deprivation therapy. Patients were required to have serum testosterone levels below 50 ng/dL during screening, except for patients with de novo small cell prostate cancer.

The composite response rate quantified by objective response per RECIST v1.1 criteria and/or prostate specific antigen reduction of at least 50% (PSA50) and/or circulating tumor count (CTC) conversion is the primary end point of phase 2a of the study, and the phase 2b primary end point is response rate in patients treated with the combination and with BXCL701 monotherapy.2 Investigators are also assessing the secondary end points of duration of response (DOR), progression-free survival, OS, and biomarker assessment as determined by changes in circulating cytokines and correlation of outcome with baseline tumor characteristics.

Additional findings from the phase 2 trial showed the combination to yield a RECIST partial response rate of 28% and a median DOR of 19 months in the phase 2 adenocarcinoma cohort. These data are in contrast to what was observed in the KEYNOTE-199 (NCT02787005) trial which evaluated pembrolizumab alone for the treatment of mCRPC. In this trial, single-agent pembrolizumab led to a 5% RECIST response rate and median DOR of 16.8 months.

“SCNC is characterized by poor prognosis and a low survival rate, and current treatment options are suboptimal,” said Vincent J. O’Neill, MD, executive vice president and chief of product development and medical officer of BioXcel Therapeutics, in a press release.¹ “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.”

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 12, 2024. http://tinyurl.com/4muk28me

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/4989whn2

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. BioXcel Therapeutics, Inc. News release. November 8, 2023. Accessed February 12, 2024. http://tinyurl.com/2eu5yyds

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