In a phase 2 trial, BXCL701 and pembrolizumab showed a significant increase in median overall survival time for patients with small cell neuroendocrine prostate cancer.
The combination of BXCL701 and pembrolizumab (Keytruda) demonstrated a median overall survival (OS) of 13.6 months compared with 7.6 months with checkpoint inhibitor monotherapy in patients with late-line refractory small cell neuroendocrine prostate cancer (SCNC).1
“OS is the most meaningful measure by which the effectiveness of an oncology treatment is evaluated. Though these results are based on a non-randomized cohort of patients, observing a median OS of this duration including patients with long-term survival at 12 months and beyond shows exceptional promise,” said Rahul Aggarwal, MD, principal investigator, associate director for clinical sciences at Helen Diller Family Comprehensive Cancer Center and professor of medicine at University of California San Francisco, in a press release.1
The open-label, multicenter, phase 2 study (NCT03910660) had an estimated enrollment of 99 patients. Its primary end point is composite response rate defined as objective response by RECIST 1.1 criteria, PSA50, and/or circulating tumor cell count conversion. Secondary end points include duration of response, progression-free survival, and OS.
Phase 1b of the trial established the recommended phase 2 dose. In phase 2, patients in the monotherapy arm received 0.3 mg of BXCL701 twice a day on days 1-14 and every subsequent 21 days, and patients in the combination arm received this dosing of BXCL701 plus 200 mg of pembrolizumab administered intravenously on day 1 every 21 days.
To be eligible to participate, patients needed evidence of progression of metastatic, castration-resistant prostate cancer; progression during or following completion of at least 1 prior line of systemic therapy; an ECOG score of 0-2; and baseline organ and hematologic function. Patients were excluded from the trial if they had received treatment with more than 2 cytotoxic chemotherapy regimens or had external beam radiation or other systemic anticancer therapy within 14 days or 5 half-lives of trial enrollment.2
“SCNC represents a major unmet medical need, with the majority of patients unfortunately succumbing to their disease in less than one year following chemotherapy. 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,” Aggarwal added.
“We believe our trial results are highly encouraging for patients with this disease and have potential implications for our evaluation of BXCL701 for the treatment of other high-grade neuroendocrine tumors, such as small cell lung cancer, where effective therapies are lacking,” said Vincent J. O’Neill, MD, chief research and development officer, OnkosXcel Therapeutics, a subsidiary of BioXcel Therapeutics, in a press release. “We intend to discuss these data with the FDA to help determine our next steps with clinical development.”1