Dr Weinberg on the Rationale for Combining BXCL701 With Pembrolizumab in mPDAC

“Pancreatic cancer is a very difficult disease to treat, and we are always looking for novel treatment options. Immunotherapy has revolutionized the treatment of many diseases but has left some patients behind especially [those with] pancreatic cancer.”

Benjamin A. Weinberg, MD, an associate professor of medicine in the Division of Hematology and Oncology of the Lombardi Comprehensive Cancer Center at Georgetown University, discussed the rationale for examining BXCL701 in combination with pembrolizumab (Keytruda) in patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) after disease progression on frontline chemotherapy.

Pancreatic cancer remains a difficult disease to treat and there is always a need for novel therapeutic approaches for these patients, Weinberg began. Progress in terms of immunotherapeutic approaches for patients with pancreatic cancer has lagged behind other disease areas and finding ways to get tumors to respond to this agent class is important for patients, he added.

Preclinical data showed that inhibiting dipeptidyl peptidase 4, 8, and 9, as well as FAP using the novel oral agent BXCL701 was synergistic with anti–PD-L1 therapy in pancreatic cancer mouse models, Weinberg explained. All these targets are overexpressed in human pancreatic cancer and the approach also downregulates intratumoral fibrosis, allowing for additional T cell infiltration into the tumor microenvironment, he added.

During the 2025 ESMO Gastrointestinal Cancers Congress, Weinberg presented date from the phase 2 EXPEL-PANC trial (NCT05558982), which evaluated the combination in patients with second-line PDAC. Findings from the study showed that the overall response rate was 17% (n = 3/18), Weinberg said. Three patients remained free from disease progression for over 6 months, he added.

In the ongoing trial, the study authors plan to incorporate pre- and on-treatment tumor biopsies in addition to collecting clinical data to evaluate if the target is being hit on a molecular level and in the tumor immune microenvironment, he concluded.