A Phase II Clinical Study of GnP Regimen (Nab-paclitaxel + Gemcitabine) Combined With Serplulimab and Stereotactic Body Radiation Therapy (SBRT) as First-line Treatment for Locally Advanced Pancreatic Cancer
This study is a single-arm phase II clinical trial. The study targets patients aged 18-75 years with ECOG performance status 0-2, diagnosed with locally advanced pancreatic ductal adenocarcinoma based on comprehensive assessment of pathology and imaging studies (CT or MRI). Participating patients will receive the GnP regimen every 21 days (nab-paclitaxel 125mg/m² ivgtt on days 1 and 8 + gemcitabine 1000mg/m² ivgtt on days 1 and 8, repeated every 21 days) combined with serplulimab (200mg ivgtt Q3W). In the second cycle, patients will receive SBRT targeting the primary tumor and/or retroperitoneal lymph nodes: 6.6Gy×5 fractions, 7Gy×5 fractions, or 8Gy×5 fractions, administered every other day with radiotherapy completed in 5 sessions (specific selection determined by investigators based on lesion size and organs at risk \[OAR\] assessment). Comprehensive evaluation including tumor markers and CT scans will be performed every 2 cycles with multidisciplinary team (MDT) review, and patients who meet surgical criteria will undergo radical resection surgery.
• Inclusion Criteria (1)Histologically confirmed pancreatic ductal adenocarcinoma with diagnosis based on comprehensive assessment of pathology and imaging studies (CT or MRI), supplemented by fibroblast activation protein positron emission tomography-computed tomography (FAPI PET-CT) when necessary, determined as locally advanced pancreatic cancer by multidisciplinary team assessment (per 2022 CSCO guideline definition) and deemed unresectable; (2)Treatment-naïve patients with no prior anticancer therapy (including chemotherapy, radiotherapy, surgery, radiofrequency ablation, irreversible electroporation, or other investigational treatments); (3)Age 18-75 years, inclusive, regardless of sex; (4)Eastern Cooperative Oncology Group (ECOG) performance status 0-2; (5)Measurable primary tumor lesions: ≥10 mm in longest diameter on spiral CT, lymph nodes ≥15 mm in short axis diameter; for conventional CT or physical examination, maximum diameter must be ≥20 mm; (6)Adequate major organ function:
‣ Bone marrow function (no blood transfusion within 14 days prior to screening): White blood cell count (WBC) ≥4.0×10⁹/L, absolute neutrophil count (ANC) ≥1.5×10⁹/L, platelet count (PLT) ≥80×10⁹/L, hemoglobin (Hb) ≥90 g/L;
⁃ Hepatic function: Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3× upper limit of normal (ULN), total bilirubin (TBIL) ≤2×ULN (for subjects with hepatic metastases: ALT and AST ≤5×ULN, TBIL ≤2×ULN), Child-Pugh score ≤7;
⁃ Renal function: Serum creatinine (Cr) ≤1.5×ULN, proteinuria ≤2+ or ≤2 g/24h, glomerular filtration rate (GFR) ≥60 mL/min/1.73 m²;
⁃ Coagulation function: Prothrombin time (PT), activated partial thromboplastin time (aPTT), and international normalized ratio (INR) ≤1.5×ULN. Patients receiving stable anticoagulation therapy for at least 30 days prior to study drug treatment may have PT or INR \>1.5×ULN if deemed appropriate for the study by investigator assessment, provided adequate justification is documented;
⁃ Serum sodium, potassium, calcium, and magnesium levels ≤Grade 1 per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0;
⁃ Electrocardiogram showing corrected QT interval (QTc) ≤480 ms; (7)No history of autoimmune disease or current autoimmune disease; (8)Life expectancy ≥3 months; (9)Signed written informed consent prior to any study-related procedures, with ability to understand the protocol and comply with study requirements.