Tislelizumab in combination with abiraterone/enzalutamide for metastatic castration-resistant prostate cancer with intraductal adenocarcinoma of the prostate after progression on prior androgen receptor pathway inhibitor.

TPS299 Background: Intraductal adenocarcinoma of the prostate (IDC-P) serves as an aggressive pathological pattern of prostate cancer. Previous retrospective study suggested limited therapeutic response of chemotherapy and androgen depriving therapy for patients with IDC-P. No standard of care treatment options are established for this type of tumor. IDC-P was characterized by genomic instability, high homologous recombination repair (HRD) scores and mutational enrichment of mismatch repair (MMR) pathway, which are predictive for response to immune checkpoint inhibitor. Tislelizumab, an investigative anti-PD-1 antibody, has demonstrated disease stabilization capacity to multiple advanced tumors. Thus in this study, we aim to investigated the efficacy and safety of tislelizumab in combination with androgen receptor pathway inhibitor (ARPI) in metastatic castration-resistant prostate cancer patients (mCRPC) after failure of first-line novel hormone therapy regimens. Methods: This is a phase II, multisite, open label study with one cohort. Eligible patients must have pathologically confirmed IDC-P. Patients with any component of neuroendocrine tumor are ineligible. Patients must have received one prior type of novel hormone therapy (e.g., abiraterone, enzalutamide) in mCRPC stage . Patients receiving chemotherapy in the mCRPC stage are excluded. Participants will receive tislelizumab 200mg IV every 21 days in combination with ARPI change (abiraterone 1000 mg PO QD+ prednisone 5 mg PO BID/enzalutamide 160 mg PO QD) for four cycles. The primary endpoint is prostate specific antigen progression-free survival (PSA-PFS) and radiographic PFS (rPFS), with key secondary endpoints including PSA response and overall survival (OS). Exploratory objectives include analyzing DNA and RNA sequencing of tumors, and measurement of ctDNA and TMB. Clinical trial information: ChiCTR2400085267 .