Adapted Guided Stereotactic Body Radiotherapy Combined With Chemotherapy and Enhancement of Novel Drug Ivonescimab for Pancreatic Cancer (ASCEND)

Inclusion criteria

• Pathologically or cytologically confirmed unresectable LAPC, as defined by the 8th edition of the American Joint Committee on Cancer (AJCC);
• Age between 18 and 80 years;
• At least one measurable pancreatic cancer lesion, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
• Life expectancy of at least 3 months;
• Adequate hematological, renal, and hepatic function, as defined by the following criteria (within 14 days prior to enrollment): (1) Hemoglobin (Hb) ≥ 90 g/L; Absolute Neutrophil Count (ANC) ≥ 1.0 × 10\^9/L; Platelet count (PLT) ≥ 75 × 10\^9/L; (2) No significant organ dysfunction, with the following criteria: Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN) or direct bilirubin ≤ ULN if total bilirubin \> 1.5 × ULN; Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; Alkaline phosphatase (ALP) ≤ 2.5 × ULN, or ≤ 2.5 × ULN for the liver fraction if ALP \> 2.5 × ULN; Serum creatinine ≤ 1.5 × ULN or calculated creatinine clearance (using the MDRD formula) ≥ 40 mL/min if serum creatinine is \> 1.5 × ULN; Urine protein \< 2+, or if ≥ 2+ on dipstick, 24-hour urine protein must be \< 2 g or the urine protein-to-creatinine ratio (UPC) must be \< 2; International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN;
• Ability to provide tissue and blood samples for translational research;
• Ability to comprehend study details and provide written informed consent.

Exclusion criteria

• History of any malignant tumors within the past 5 years, except for cured localized tumors;
• Uncontrolled infections (e.g., active tuberculosis or hepatitis), uncontrolled systemic diseases, poorly controlled hypertension or diabetes, or severe comorbidities within the past six months, including myocardial infarction, cerebral embolism, or significant arrhythmias;
• Previous treatment with drugs targeting other stimulatory or co-inhibitory T-cell receptors;
• Prior radiotherapy within 2 weeks before enrollment;
• Known allergy to Ivonescimab or its excipients;
• Pregnancy or lactation;
• Current or planned use of strong CYP3A4/5 or CYP1A2 inducers or strong CYP3A4/5 inhibitors;
• Requirement for oral vitamin K antagonists for anticoagulation. Low-dose warfarin (≤ 2 mg/day) and other low-dose anticoagulants for maintaining central venous access or preventing deep vein thrombosis are permitted. Low-molecular-weight heparin is also permitted;
• Conditions affecting oral medication administration, such as a history of gastrointestinal perforation or fistula within the past 6 months, history of intestinal obstruction, extensive bowel resection, Crohn's disease, ulcerative colitis, or chronic diarrhea.