A phase Ib/II trial of XL888 (HSP90 inhibitor) and pembrolizumab in metastatic pancreatic cancer with translational immune profiling.

ABSTRACT: Pancreatic adenocarcinoma is marked by high mortality and limited treatment options. In mice, HSP90 inhibition limits cancer-associated fibroblasts activation and enhances T cell infiltration, sensitizing tumors to PD-1 blockade. We hypothesized that co-administration of pembrolizumab (anti-PD-1) with XL888 (an HSP90 inhibitor) would be safe and induce measurable immunological changes in the PDAC tumor microenvironment that could influence clinical outcome. We report results from an expansion cohort of patients with advanced PDAC (n = 16), who were enrolled in a single-center, open-label, nonrandomized, dose-escalation study. Patients received one cycle of either pembrolizumab (200 mg) alone or in combination with XL888 (90 mg, orally twice per week) over a 21-day cycle, followed by crosso

SUBMITTER: Horvat NK 

PROVIDER: S-EPMC12781125 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature