GnP plus serplulimab with stereotactic body radiation therapy for first-line locally advanced pancreatic cancer.

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 trial will test whether combining GnP chemotherapy, the immunotherapy serplulimab, and focused SBRT helps people aged 18–75 with untreated, locally advanced pancreatic ductal adenocarcinoma.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 23 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: West China Hospital (Academic / other)
• Drugs / interventions: ipilimumab, chemotherapy, immunotherapy, radiation, prednisone, serplulimab
• Locations: 1 site (Chengdu, Sichuan)
• Trial ID: NCT07101679 on ClinicalTrials.gov

What this trial studies

This is a single-arm phase II trial at West China Hospital enrolling treatment-naïve adults with locally advanced, unresectable pancreatic ductal adenocarcinoma. Participants receive the GnP regimen (nab-paclitaxel 125 mg/m² IV on days 1 and 8 plus gemcitabine 1000 mg/m² IV on days 1 and 8, repeated every 21 days) combined with serplulimab 200 mg IV every 3 weeks. SBRT to the primary tumor and/or retroperitoneal nodes is delivered during the second cycle using one of three fractionation options (6.6 Gy × 5, 7 Gy × 5, or 8 Gy × 5) given every other day over five sessions based on lesion size and organs-at-risk. Tumor markers and CT scans are obtained every two cycles with multidisciplinary team review to monitor response and consider conversion to resection.

Who should consider this trial

Good fit: Ideal candidates are treatment-naïve adults aged 18–75 with pathologically confirmed, locally advanced unresectable pancreatic ductal adenocarcinoma, ECOG 0–2, and measurable lesions meeting the size criteria.

Not a fit: Patients with metastatic disease, prior anticancer therapy, ECOG performance status >2, or significant comorbidities that preclude chemotherapy, immunotherapy, or SBRT are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the regimen could improve local tumor control and may increase the chance that some unresectable tumors become surgically removable, potentially improving outcomes.

How similar studies have performed: Chemotherapy combined with SBRT has shown improved local control in some prior studies, but adding PD-1–axis immunotherapy like serplulimab in pancreatic cancer is relatively novel and has limited prior evidence of success.

Eligibility criteria

Inclusion Criteria:

1. 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.

Exclusion Criteria:

1. Known hypersensitivity or allergy to any of the study drugs;
2. Patients with distant metastatic disease classified as Stage IV pancreatic cancer;
3. Patients whose tumor lesions are determined by the surgical team or multidisciplinary team to be resectable or borderline resectable pancreatic cancer based on imaging studies (CT or MRI) (per 2022 CSCO guideline definition);
4. Patients whose lesions are deemed unsuitable for stereotactic body radiation therapy (SBRT) by investigator assessment;
5. Known or suspected central nervous system (CNS) metastases, defined as subjects with signs or symptoms suggestive of CNS metastases, unless CNS metastases have been excluded by CT or MRI;
6. History of other malignancies within 5 years (except adequately treated basal cell carcinoma of the skin and cervical carcinoma in situ);
7. Requirement for concurrent anticancer treatments other than the study treatment regimen during the study period, including chemotherapy, targeted therapy, hormonal therapy, immunotherapy regimens, radiotherapy, or traditional Chinese medicine with anticancer properties;
8. Prior or current use of chemotherapy, focal adhesion kinase (FAK) inhibitors, or anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) antibodies (including ipilimumab or any other antibody or drug targeting T-cell co-stimulation or checkpoint pathways);
9. Diagnosis of immunodeficiency or receiving chronic systemic corticosteroid therapy (daily dose exceeding 10 mg prednisone or equivalent) or any other form of immunosuppressive treatment within 7 days prior to first study drug administration;
10. Receipt of live vaccines within 30 days prior to first study drug treatment (including but not limited to: measles, mumps, rubella, varicella/zoster, yellow fever, rabies, bacillus Calmette-Guérin \[BCG\], and typhoid vaccines). Inactivated vaccines such as injectable seasonal influenza vaccines are permitted, but live attenuated vaccines such as intranasal influenza vaccines (e.g., FluMist) are not allowed;
11. Uncontrolled hypertension (defined as systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>100 mmHg despite treatment);
12. Significant cardiac disease, including congestive heart failure (New York Heart Association \[NYHA\] Class III-IV), prior myocardial infarction, or uncontrolled angina within 6 months;
13. Cardiac arrhythmias requiring treatment, including atrial fibrillation, supraventricular tachycardia, ventricular tachycardia, or ventricular fibrillation; confirmed ECG abnormalities deemed by the investigator to require clinical intervention or treatment;
14. History of hemorrhagic or thromboembolic events within 6 months, such as cerebrovascular accident (including transient ischemic attack), pulmonary embolism, or spontaneous major tumor bleeding;
15. Need for surgical treatment within 28 days before or anticipated within 28 days after the last study drug administration;
16. Presence of poorly controlled third-space fluid collections, such as large pleural effusions or ascites;
17. istory of gastrointestinal perforation or suspected risk of gastrointestinal perforation;
18. Investigator determination that concomitant medications required during the study period may affect study drug metabolism, such as strong CYP3A4 inhibitors or inducers, drugs primarily metabolized by CYP3A4, 2C8, 2C9, 2C19, or 2D6 with narrow therapeutic indices;
19. Severe psychiatric disorders;
20. Pregnancy, potential pregnancy, or lactation;
21. Subjects of childbearing potential unwilling to use contraception during the study period and for 3 months after the last study drug administration;
22. Participation in other drug or medical device clinical trials within 4 weeks prior to study entry;
23. Any condition deemed inappropriate for study participation by investigator judgment.

Where this trial is running

Chengdu, Sichuan

• West China Hospital, Sichuan University — Chengdu, Sichuan, China (Recruiting)

Study contacts

• Principal investigator: Dan Cao, MD — Division of Abdominal Tumor, Department of Medical Oncology, Cancer Center and State Key Laboratory of Biological Therapy, West China Hospital, Sichuan University, Chengdu, Sichuan
• Study coordinator: Dan Cao, MD

Conditions Locally Advanced Pancreatic Ductal Adenocarcinoma; SBRT; serplulimab