(UroToday.com) On the first day of the American Society for Clinical Oncology (ASCO) Genitourinary Cancer Symposium 2022, Poster Session A focussed on the care of patients with prostate cancer. Dr. Tagawa presented a poster describing the use of BXCL701 in patients with metastatic castration-resistant prostate cancer (mCRPC) who have a small-cell neuroendocrine carcinoma (SCNC) phenotype. This SCNC phenotype is associated with aggressive disease biology and androgen independence as it does not express androgen receptor or PSA.
BXCL701, also known as talabostat, is an oral small molecule inhibitor of dipeptidyl peptidases (DPP)—primarily DPP 8/9 & DPP 4— which triggers inflammasome to alert and prime immune cells. This leads to induction of IL-18 & IL-1ß, bridging innate & adaptive immunity.
To be eligible for this phase 2a study, patients with metastatic prostate cancer with SCNC histopathological features, either de novo or treatment-emergent including mixed SCNC, were required to have progression by PCWG3 on ≥1 prior line of cytotoxic chemotherapy (patients who either have refused chemotherapy or are considered unsuitable for chemotherapy may be considered eligible following discussion with the sponsor). Patients also had to have ECOG performance status of 0-2 and measurable disease per RECIST 1.1. Notably, patients were excluded if they had previously received an immune checkpoint inhibitor or more than 2 prior regimes of cytotoxic chemotherapy.
Following enrollment, patients received pembrolizumab (200 mg IV q21-days) and BXCL701 0.2 mg BID for a week with step-up to 0.3 mg BID on days 8-14, and 0.3 mg BID on days 1-14 of subsequent cycles. The primary endpoint of interest is Composite Response, defined as RECIST 1.1 ± PSA50 ± CTC count conversion. The phase 2 component of this study uses a Simon 2-stage minimax design with 15 evaluable patients in stage 1 and 13 in stage 2.
As of a data cut-off of November 24, 2021, 18 patients were enrolled of whom 15 were evaluable. The mean time of prior treatment regimes was 2.3 (SD 1.1). Nearly all (93%) of patients had received platinum chemotherapy. The median duration of therapy was 9 weeks (range 2 to 26 weeks).
With a follow-up ranging to January 21, 2022, the composite response rate was 33% with 3 patients having partial response (among 12 who were RECIST evaluable). Additionally, 3 patients had stable disease for an overall disease control rate of 58%. Only one of three CTC evaluable patients had a CTC response.
In general, BXCL701 with pembrolizumab was acceptably tolerated without evidence of increased immune-related AEs compared to historic controls with checkpoint inhibitors. AEs consistent with cytokine activation were observed (hypotension, fever, fatigue). Only three patients had serious adverse events potentially related to study therapy.
Thus, in conclusion, oral BXCL701 in combination with pembrolizumab demonstrates promising anti-tumor activity and reasonable toxicity in very late-line, refractory mCRPC SCNC for which there is currently no standard of care.Presented by: Scott T. Tagawa FACP, MD, MS, Weill Cornell Medicine, New York, NY