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

Prior treatment

• Known hypersensitivity to the investigational drug or any of its excipients.
• Major surgery, open biopsy, or significant traumatic injury within 4 weeks before study treatment.
• Participation in another investigational drug clinical study within 4 weeks before enrollment.
• Any of the following medical conditions: Untreated or symptomatic brain metastases or spinal cord compression. Other active malignancy requiring concurrent treatment.
  • Active autoimmune disease or immunodeficiency, or a history of such conditions, including autoimmune hepatitis, interstitial pneumonia, uveitis, rheumatoid arthritis, inflammatory bowel disease, hypophysitis, vasculitis, or nephritis. Exceptions include stable conditions not requiring systemic immunosuppressive therapy, such as type 1 diabetes mellitus, hypothyroidism requiring only hormone replacement therapy, or skin diseases not requiring systemic treatment, such as vitiligo, psoriasis, or alopecia. History of substance abuse or psychiatric disorders that may interfere with study participation.
• Severe infection within 4 weeks before the first dose, including infectious complications, bacteremia, or severe pneumonia requiring hospitalization or intravenous antibiotics, antifungal agents, or antiviral therapy; or unexplained fever \>38.5°C during screening or before the first dose.

Other illness

• History of other malignancy within the past 5 years, except for malignancies that have been definitively treated and are considered cured.
• Any other condition that, in the investigator's judgment, may prevent the participant from complying with study procedures, restrictions, or requirements.

Lab values

• Severe and/or uncontrolled medical conditions, including: Uncontrolled hypertension, defined as systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg. Grade ≥1 myocardial ischemia or myocardial infarction; clinically significant arrhythmia, including QTc ≥450 ms in males or ≥470 ms in females; congestive heart failure of NYHA class ≥II; or LVEF \<50%. Decompensated diabetes mellitus or other conditions contraindicating high-dose corticosteroid therapy. Exacerbation of chronic obstructive pulmonary disease (COPD) or other severe respiratory disease requiring hospitalization. Active or uncontrolled severe infection (≥Grade 2 according to CTCAE). Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage. Cirrhosis, decompensated liver disease, active hepatitis, or chronic hepatitis requiring antiviral treatment. Renal dysfunction with urine protein ≥++ on urinalysis and confirmed 24-hour urinary protein \>1.0 g.

Other

• Active brain metastases or leptomeningeal metastases at enrollment.
• Acute pancreatitis meeting diagnostic criteria or subclinical pancreatitis requiring recent intervention.

• Age 18 to 75 years, male or female.
• Histologically or cytologically confirmed unresectable locally advanced or metastatic pancreatic cancer.
• ECOG Performance Status of 0 or 1.
• Disease progression after first-line systemic therapy.
• At least one measurable lesion according to RECIST 1.1, as assessed by the investigator.
• Availability of 10 archived tumor tissue sections and 10 mL of peripheral blood.
• Adequate organ function.
• Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days before enrollment, must not be breastfeeding, and must agree to use effective contraception during the study and for 6 months after the end of study treatment. Male participants must also agree to use effective contraception during the study and for 6 months after the end of study treatment.
• Voluntary participation in the study, provision of written informed consent, and willingness and ability to comply with study procedures and follow-up.