This is a prospective, open-label, single-arm clinical study designed to evaluate the efficacy and safety of retlirafusp alfa combined with apatinib and chemotherapy as second-line treatment in patients with unresectable locally advanced or metastatic pancreatic cancer who have experienced disease progression after first-line systemic therapy. Approximately 37 participants will be enrolled. 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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
37
Retlirafusp alfa will be administered in combination with apatinib and fluoropyrimidine-based chemotherapy as second-line treatment for locally advanced or metastatic pancreatic cancer.
Apatinib will be administered in combination with retlirafusp alfa and fluoropyrimidine-based chemotherapy as second-line treatment for locally advanced or metastatic pancreatic cancer.
Fluoropyrimidine-based chemotherapy selected at the investigator's discretion will be administered in combination with retlirafusp alfa and apatinib as second-line treatment for locally advanced or metastatic pancreatic cancer.
Progression-free survival
Progression-free survival (PFS) is defined as the time from the first administration of study treatment to the date of disease progression, as assessed by the investigator, or death from any cause, whichever occurs first.
Time frame: Progression-free survival (PFS) will be assessed by the investigator according to RECIST 1.1, for up to 2 years after the first administration of study treatment.
Overall Survival
Overall survival (OS) is defined as the time from the first administration of study treatment to death from any cause.
Time frame: Up to 3 years after the first administration of study treatment.
Objective response rate
Per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) using Investigator assessments, is defined as the number (%) of patients with response of Complete Response or Partial Response, will be assessed up to 1 years.
Time frame: Data obtained up until progression, or the last evaluable assessment in the absence of progression, will be assessed up to 1 years
Duration of Response
Duration of Response(DoR)refers to the time from the first assessment as CR or PR to the first assessment as PD or (due to any reason) death.
Time frame: Duration of Response(DoR)analysis based on investigator assessment per RECIST 1.1, and will be assessed up to 1 years.
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