BXCL701 Plus Pembrolizumab Improves OS in mCRPC

Conceptual image for prostate cancer treatment, 3D illustration showing destruction of a tumor inside prostate gland: ©Dr_Microbe - stock.adobe.com

The combination of BXCL701, an oral innate immune activator, and pembrolizumab (Keytruda) demonstrated a median overall survival (OS) of 15.5 months (95% CI, 9.6-not evaluable) in patients with metastatic castration-resistant prostate cancer (mCRPC) of the adenocarcinoma phenotype, according to BioXcel Therapeutics, BXCL701’s manufacturer.¹

Findings come from a phase 2 trial (NCT03910660) evaluating the drug combination in patients with mCRPC. This OS is an improvement compared with an OS of 9.6 months with checkpoint inhibitor monotherapy, as observed in a separate phase 2 trial in late-line refractory patients. The study also demonstrated a 12-month survival rate of 59% as of the data cutoff of September 6, 2023.

In addition to the OS data, BioXcel reported a RECIST partial response rate of 28% and a median duration of response (DOR) of 19 months in the phase 2 adenocarcinoma cohort. These data are in contrast of what was observed in the KEYNOTE-199 (NCT02787005) trial of pembrolizumab as a single agent in mCRPC. Here, single-agent pembrolizumab demonstrated a 5% RECIST response rate and median DOR of 16.8 months.

“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,” Vincent J. O’Neill, MD, chief research and development officer, OnkosXCel, in a press release.¹

3D rendered medically accurate illustration of prostate cancer: ©SciePro - stock.adobe.com

About the Phase 2 Trial of BXCL701 and Pembrolizumab

The trial is a phase 1b/2, open-label, multicenter study evaluating the recommended phase 2 dose and assessing the efficacy and safety or orally administered BXCL701 as a single agent and in combination with pembrolizumab. The study has an enrollment of 98 patients. Patients were randomized to receive BXCL701 daily on days 1-14 of a 21-day cycle with or without 200 mg of intravenous pembrolizumab on day 1 of the cycle.²

The phase 2a primary end point is composite response rate of the drug combination, and the phase 2b primary end point is response rate in patients treated with the combination and with BXCL701 monotherapy. Secondary end points for phase 2a include median radiographic progression-free survival (rPFS), median prostate-specific antigen (PSA), PFS, median OS, median DOR, risk profile of BXCL701, population pharmacokinetics, and pharmacokinetic profile. The secondary end points for phase 2b are complete response rate, OS, DOR, rPFS, and PSA PFS.

Inclusion criteria consisted of evidence of progressive mCRPC defined by PCWG3 criteria following at least 1 prior line of therapy, an ECOG performance status of 0-2, ≥18 years of age, and adequate baseline organ function. Patients are not eligible to participate if they have received more than 2 cytotoxic chemotherapy regimens, external beam radiation within 14 days or 5 half-lives of study treatment, or anti-PD(L)1 agents.

“Patients with mCRPC who have failed androgen deprivation and taxane-based chemotherapy have few remaining treatment options and, unfortunately, [pembrolizumab] to date has not shown additional benefit in this setting. Therefore, we are highly encouraged by these combination data bearing in mind historical data with checkpoint inhibitor monotherapy,” O’Neill added in a press release.¹

REFERENCES:

1. BioXcel Therapeutics reports positive overall survival results from single-arm, open-label phase 2 trial of BSCL701 in patients with metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma phenotype. News release. BioXcel Therapeutics. November 8, 2023. Accessed November 8, 2023. https://tinyurl.com/cu46rw69

2. 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. Accessed November 8, 2023. https://clinicaltrials.gov/study/NCT03910660