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A Phase 1b/2 Study of BXCL701, a Small Molecule Inhibitor of Dipeptidyl Peptidases (DPP), Administered in Combination with the Anti-Programmed Cell Death 1 (PD-1) Monoclonal Antibody Pembrolizumab (PEMBRO; Keytruda®) in Patients with Small Cell Neuroendocrine Prostate Cancer (SCNC; NEPC)
An open-label, multicenter, Phase 1b/2 study to determine the composite response rate of BXCL701 administered orally and daily, combined wit PEMBRO, in patients with Small Cell Neuroendocrine Prostate Cancer(SCNC). This study will also assess other efficacy parameters as well as the safety of the combined treatment. This study will consist of two (2) stages. Lead-in Stage, in which the safety and tolerability of the combination will be assessed and confirmed. And the Efficacy Stage, in which patients with SCNC will be treated with BXCL701 combined with PEMBRO.
Primary objectives of the study are: - To estimate the composite response rate of the combination of BXCL701 + PEMBRO in patients with SCNC. Composite response rate is defined as achieving 1 or more of the following: o Objective response by Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria o Circulating tumor cell (CTC) conversion from >5/7.5 mL to <5/7.5 mL per Veridex assay by completion of Week 12 of protocol therapy o Greater than 50% prostate-specific antigen (PSA) decline from baseline by completion of Week 12 of protocol therapy Secondary Objectives The secondary objectives of the study include: - To estimate the median radiographic progression-free survival (rPFS) of the combination of BXCL701 and PEMBRO in patients with SCNC. - To estimate the median PSA progression-free survival (PSA PFS) of the combination of BXCL701 and PEMBRO in patients with SCNC. - To estimate the median overall survival (OS) of the combination of BXCL701 and PEMBRO in patients with SCNC. - To estimate the median duration of response (DOR) of the combination of BXCL701 and PEMBRO in patients with SCNC. To continue to characterize the safety profile of BXCL701 in combination with PEMBRO. - To assess population pharmacokinetics of BXCL701 using sparse pharmacokinetic sampling. - To assess the pharmacodynamic profile of the combination of BXCL701 and PEMBRO by measuring relevant effects on those cytokines previously shown to be modulated by BXCL701 in humans. Exploratory Objectives - To determine the response rate by Immune Response Evaluation Criteria In Solid Tumors (iRECIST) criteria with BXCL701 in combination with PEMBRO. - To evaluate the quantitative and qualitative effects of BXCL701 in combination with PEMBRO on relevant immune effector cytokines and various immunological effector cells, including neutrophils, myeloid derived suppressor cells (MDSCs), dendritic cells, cancer associated fibroblast (CAF) and T-cells in blood and, whenever feasible, in tumor tissues. - To explore the predictive value of baseline programmed death-ligand 1 (PD-L1) tumor expression in metastatic tumor tissue and CTCs with subsequent clinical outcomes - To explore the relationship between baseline and on-treatment circulating tumor neoantigens and T-cell repertoire and clinical outcomes (Central Laboratory) - To explore the relationship between baseline tumor messenger ribonucleic acid (mRNA) immune profiling panel and clinical outcomes.