Clinical Study of Radiotherapy Combined With Adebrelimab and NALIRIFOX for Conversion Therapy in Locally Advanced Pancreatic Cancer

Inclusion Criteria:

• Signed informed consent form

Age 18-75 years

Histologically or cytologically confirmed pancreatic ductal adenocarcinoma

Locally advanced disease as determined by the investigator (with reference to the CSCO Clinical Practice Guidelines for Pancreatic Cancer)

No prior treatment for pancreatic cancer, including radiotherapy, chemotherapy, or surgery

At least one measurable lesion according to RECIST v1.1 criteria

ECOG performance status score of 0-1

Adequate organ function based on laboratory tests performed within 28 days prior to the first dose:

1. Complete blood count:

   Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L Platelet count ≥ 75 × 10⁹/L Hemoglobin ≥ 90 g/L

2. Blood biochemistry:

   Serum albumin ≥ 30 g/L Serum total bilirubin ≤ 1.5 × ULN ALT and AST ≤ 3 × ULN Serum creatinine (Cr) ≤ 1.5 × ULN; or creatinine clearance calculated by the Cockcroft-Gault formula > 50 mL/min

3. International normalized ratio (INR) ≤ 1.2, or prothrombin time (PT) exceeding the normal range by ≤ 2 seconds
4. Urine protein < 2+ (if urine protein ≥ 2+, 24-hour urine protein quantification is required; patients with 24-hour urine protein < 1.0 g are eligible) Male subjects and female subjects of childbearing potential must use contraceptive measures from the first dose until 6 months after the last dose of the study drug

Exclusion Criteria:

• Presence of distant metastasis

Contraindications to surgical resection of pancreatic cancer

History of another malignancy other than pancreatic cancer within 5 years prior to enrollment, or concurrent malignancy at the time of enrollment

Prior allogeneic stem cell transplantation or solid organ transplantation

Symptomatic active central nervous system (CNS) metastases and/or carcinomatous meningitis, or uncontrolled major seizure disorder, unless ruled out by CT or MRI

History of uncorrectable electrolyte disturbances, including serum potassium, calcium, or magnesium abnormalities

Current interstitial pneumonia or interstitial lung disease, history of interstitial pneumonia or interstitial lung disease requiring corticosteroid therapy, or any other condition that may interfere with the assessment and management of immune-related pulmonary toxicity; active pulmonary tuberculosis

Active autoimmune disease or history of autoimmune disease with potential for recurrence

Use of immunosuppressive agents or systemic corticosteroids for the purpose of immunosuppression within 2 weeks prior to enrollment

Active infection, unexplained fever ≥ 38.5°C within 1 week prior to enrollment, or baseline white blood cell count > 15 × 10⁹/L; use of oral or intravenous therapeutic antibiotics within 2 weeks prior to enrollment

Congenital or acquired immunodeficiency (e.g., HIV infection)

Receipt of a live attenuated vaccine within 4 weeks prior to enrollment, or anticipated need for such vaccination during adebrelimab treatment or within 60 days after the last dose

Clinically significant bleeding symptoms or evident bleeding tendency within 6 months prior to enrollment; known hereditary or acquired bleeding tendency or thrombotic tendency

Major vascular disease, arterial thromboembolism

Uncontrolled or poorly controlled cardiac clinical symptoms or disease, such as:

1. New York Heart Association (NYHA) Class > II heart failure, or left ventricular ejection fraction (LVEF) < 50% as assessed by color Doppler echocardiography
2. Unstable angina pectoris
3. Myocardial infarction within 1 year prior to initiation of study treatment
4. Clinically significant supraventricular or ventricular arrhythmia requiring treatment or intervention
5. QTc interval > 450 ms (males) or > 470 ms (females) (QTc calculated using Fridericia's formula; if the QTc value is abnormal, measurements should be repeated three times at 2-minute intervals and the average value taken) Uncontrolled pleural effusion, pericardial effusion, or moderate or greater ascites

Hypertension not adequately controlled with antihypertensive medication (systolic blood pressure ≥ 140 mmHg or diastolic blood pressure ≥ 90 mmHg); history of hypertensive crisis or hypertensive encephalopathy

Presence of severe, non-healing or dehisced wounds, active ulcers, or untreated fractures

Major surgery (excluding diagnostic surgery) within 4 weeks prior to enrollment, or planned major surgery during the study period

History of intestinal obstruction and/or clinical symptoms or signs of gastrointestinal obstruction within 6 months prior to enrollment

Known allergy or hypersensitivity to any study drug or excipient

Participation in another clinical study of an investigational drug within 4 weeks prior to enrollment

Pregnant or breastfeeding women

Other factors that, in the opinion of the investigator, render the subject unsuitable for study participation