Talabostat and Pembrolizumab for the Treatment of Advanced Solid Cancers

PRIMARY OBJECTIVES: I. To evaluate response rate per Response Evaluation Criteria in Solid Tumors (RECIST) and immune (i)RECIST in patients treated in cohort A and in patients treated in cohort B. II. To evaluate dose-limiting toxicities (DLT) in the first 6 patients enrolled to the study. SECONDARY OBJECTIVES: I. To evaluate progression-free survival (PFS). II. To evaluate duration of response (DOR). III. To evaluate overall survival (OS). IV. To evaluate overall safety and tolerability. EXPLORATORY OBJECTIVES: I. To evaluate the quantitative and qualitative effects of talabostat (BXCL701) in combination with pembrolizumab on relevant immune effector cytokines in blood. II. To evaluate the quantitative and qualitative effects of BXCL701 in combination with pembrolizumab on various immunological effector cells, including neutrophils, myeloid derived suppressor cells (MDSCs), dendritic cells, cancer associated fibroblast (CAF), T-cells and macrophage density in pre-dose tumor biopsies and when feasible in post-dose tumor tissues. III. To explore the predictive value of baseline programmed death ligand 1 (PD-L1) tumor expression and tumor mutation burden (TMB) with clinical outcomes. IV. To evaluate changes in serially collected blood circulating tumor deoxyribonucleic acid (DNA) (ctDNA) to assess for tumor response and clonal evolution. V. To evaluate pre- and post-treatment PD-L1 positron emission tomography (PET)/computed tomography (CT) as a predictive tool for therapeutic efficacy. OUTLINE: Patients receive talabostat orally (PO) twice daily (BID) on days 1-14 and pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days.