Retlirafusp Alfa Plus Apatinib and Chemotherapy as Second-Line Treatment for Pancreatic Cancer

Pancreatic cancer is an aggressive malignancy with a poor prognosis. Most patients are diagnosed with unresectable locally advanced or metastatic disease, and treatment options after progression on first-line systemic therapy remain limited. Pancreatic cancer is characterized by an immunosuppressive tumor microenvironment and dense desmoplastic stroma. TGF-β contributes to immune suppression and stromal remodeling, while PD-L1-mediated signaling promotes immune evasion. Retlirafusp alfa is a bifunctional fusion protein targeting PD-L1 and TGF-β receptor II (TGF-βRII), designed to simultaneously inhibit PD-L1/PD-1 signaling and TGF-β signaling. This prospective, open-label, single-arm study will evaluate the efficacy and safety of retlirafusp alfa combined with apatinib and fluoropyrimidine-based chemotherapy, with the specific chemotherapy regimen selected by the investigator, as second-line treatment for patients with unresectable locally advanced or metastatic pancreatic cancer after progression on first-line systemic therapy. Approximately 37 participants will be enrolled. Study treatment will continue until disease progression, unacceptable toxicity, withdrawal of informed consent, or other treatment discontinuation criteria are met. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DOR), and safety.