Surufatinib Plus mFOLFIRINOX and PD-1 Inhibitor as the Neoadjuvant Therapy for High-risk or Borderline Resectable Pancreatic Cancer

Neoadjuvant Therapy With Surufatinib Combined With mFOLFIRINOX and Toripalimab for High-risk or Borderline Resectable Pancreatic Cancer: A Phase II, Single-arm, Single-center Study

The goal of this clinical trial is to learn if surufatinib (VEGFR-TKI) plus toripalimab (PD-1 inhibitor) and mFOLFIRINOX (chemotherapy) works as neoadjuvant therapy for patients with high-risk or borderline resectable pancreatic cancer. It will also learn about the safety of the combination regimen. The main questions it aims to answer are:

Does the treatment regimen of surufatinib combined with immunotherapy and chemotherapy could provide further survival benefits for patients with high-risk resectable or borderline resectable pancreatic cancer as neoadjuvant therapy?

Is the safety of this combination therapy tolerable?

Participants will:

Take surufatinib (200mg, qd, po, q2w), Toripalimab (3mg/kg, iv, d1, q2w), Oxaliplatin (68 mg/m², iv, d1, q2w), Irinotecan (135 mg/m², iv, d1, q2w), Calcium folinate (400 mg/m², iv, d1, q2w), 5-FU (2400 mg/m², iv). Treatment for up to 8 cycles.

Visit the clinic once every 8 weeks (± 7 days) for checkups and tests. Keep a diary of their symptoms and record daily medication doses.

Study Overview

• Status: Not yet recruiting
• Conditions: Pancreatic Cancer Resectable
• Intervention / Treatment: Drug: Surufatinib; Drug: Toripalimab; Drug: mFOLFIRINOX

Detailed Description

This study is a single-center, single-arm, phase II study.

Preoperative neoadjuvant treatment plan:

• Surufatinib: 200 mg orally once daily, continuous dosing, with a 14-day treatment cycle;
• Toripalimab: 3 mg/kg per dose, intravenous infusion over 1 hour on day 1, every 14 days per treatment cycle;
• Oxaliplatin: 68 mg/m² intravenous infusion over 2 hours on day 1;
• Irinotecan: 135 mg/m² intravenous infusion over 30-90+ minutes on day 1;
• Calcium folinate: 400 mg/m² intravenous infusion over 2 hours on day 1;
• 5-FU: 2400 mg/m² continuous intravenous infusion over 46 hours; repeated every 14 days per treatment cycle.

Neoadjuvant treatment will be administered for up to 8 cycles. During treatment, tumor assessments using imaging will be conducted every 8 weeks (±7 days). For patients achieving stable disease, partial response, or complete response, it will be evaluated whether surgery is feasible. Surgery should occur at least 2 weeks after the last neoadjuvant treatment.

Postoperative adjuvant treatment plan:

• Adjuvant treatment will begin within 4-8 weeks after surgery, with the specific regimen determined by the investigator.
• During postoperative adjuvant treatment, tumor assessments using imaging will be conducted every 8 weeks (±7 days) until disease progression (RECIST 1.1) or death (during patient treatment), or until intolerable toxicity occurs. Subsequent treatment after disease progression and survival status will also be recorded.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zhiqiang Wang, Phd; Phone Number: 020-87343289; Email: wangzhq@sysucc.org.cn

Study Locations

• China
  • Guangzhou, China
    • Sun Yat-sen University Cancer Center
    • Contact: Zhiqiang Wang, Phd; Phone Number: 020-87343289; Email: wangzhq@sysucc.org.cn
    • Principal Investigator: Zhiqiang Wang, Phd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Voluntarily sign the informed consent form.
2. Ages 18-75 years, no gender restrictions.

3. Patients with high-risk resectable or borderline resectable pancreatic cancer confirmed by pathological tissue or cytology:

   • High-risk features include: ① Imaging findings; ② Significant elevation of CA 19-9 (baseline >210 U/ml, Vincent P Groot, Ann Surg. 2019 Jun;269(6):1154-1162); ③ Large primary tumor (>3 cm, Vincent P Groot, Ann Surg. 2019 Jun;269(6):1154-1162); ④ Large regional lymph nodes (it is recommended to use imaging to assess lymph node metastasis, or if the number of metastatic lymph nodes >3, N2 stage); ⑤ Excessive weight loss (more than 5 kg within 1 month); ⑥ Severe pain (main complaint of abdominal pain is sufficient).
   • Definition of borderline resectable: ① Arteries: Tumor contact with the celiac trunk (≤180°) or superior mesenteric artery (SMA) (≤180°), or involvement of the hepatic artery that is reconstructable. ② Veins: Narrowing or occlusion of the superior mesenteric vein (SMV)/portal vein (PV), but the proximal/distal vessels are suitable for reconstruction.
4. The patient must have at least one measurable lesion (RECIST 1.1).
5. No BRCA1/2 or PALB2 mutations.
6. Has not previously received systemic therapy or local radiotherapy.
7. ECOG performance status 0-1;
8. Expected survival ≥24 weeks;
9. No surgical contraindications;
10. Blood tests (without transfusion in the past 14 days) 1) Absolute neutrophil count ≥1.5×10⁹/L, platelets ≥100×10⁹/L, hemoglobin concentration ≥9 g/dL; 2) Liver function tests (AST and ALT ≤2.5×ULN, total bilirubin ≤1.5×ULN; if there are liver metastases, AST and ALT ≤5×ULN); 3) Kidney function (serum creatinine ≤1.5×ULN, creatinine clearance (CCr) ≥60 ml/min); 4) Coagulation, international normalized ratio (INR) ≤1.5×ULN, prothrombin time (PT) and activated partial thromboplastin time (APTT) ≤1.5×ULN;
11. Male or female patients of reproductive potential voluntarily use effective contraception during the study period and for 6 months after the last study treatment, such as dual-barrier contraceptive methods, condoms, oral or injectable contraceptives, intrauterine devices, etc. All female patients will be considered of reproductive potential unless the female patient is naturally menopausal, has undergone induced menopause, or has had sterilization procedures (such as hysterectomy, bilateral salpingo-oophorectomy, or ovarian irradiation).

Exclusion Criteria:

1. Patients with distal metastasis;
2. Received blood transfusion therapy, blood products and hematopoietic factors such as albumin and granulocyte colony-stimulating factor (G-CSF) within 14 days before enrollment;
3. Received any surgical or invasive treatment or operation within 4 weeks prior to enrollment (except for intravenous catheterization, puncture and drainage, etc.);
4. Known allergy to any drug in the study;
5. Presence of hypertension that cannot be controlled by medication, as prescribed as: systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg;
6. The patient currently has any disease or condition that affects the absorption of the drug, or the patient has difficulty swallowing and cannot take surufatinib orally;
7. Patients currently have active gastric and duodenal ulcers, ulcerative colitis and other gastrointestinal diseases or active bleeding from unresected tumors, or other conditions that may cause gastrointestinal bleeding or perforation as determined by the investigator;
8. Uncontrollable malignant ascites (defined as ascites that cannot be controlled by diuretics or puncture methods as judged by the investigator);
9. Patients with obvious evidence or history of bleeding tendency within 3 months before enrollment (bleeding >30 mL within 3 months, with hematemesis, black feces, blood in the stool), hemoptysis (>5 mL of fresh blood within 4 weeks), or thromboembolic events (including stroke events and/or transient ischemic attack) within 10 months;
10. Clinically significant electrolyte abnormalities judged by the investigator;
11. Significant clinically significant cardiovascular disease, including but not limited to the following: acute myocardial infarction, severe/unstable angina, or coronary artery bypass grafting within 6 months before enrollment; Congestive heart failure New York Heart Association (NYHA) grade >2; ventricular arrhythmias requiring medication; LVEF (left ventricular ejection fraction) < 50%;
12. Other malignant tumors within the past 5 years, except basal cell or squamous cell carcinoma of the skin after radical surgery, or carcinoma in situ of the cervix;
13. Active or uncontrolled serious infection:

1) Known human immunodeficiency virus (HIV) infection; 2) Known history of clinically significant liver disease, including viral hepatitis [for known hepatitis B virus (HBV) carriers, active HBV infection must be excluded, i.e., HBV DNA positive (>1×10^4 copies/mL or >2000 IU/mL)]; 3) Known hepatitis C virus (HCV) infection with HCV RNA positive (>1×10^3 copies/mL), or other hepatitis, cirrhosis; 14. Women who are pregnant (tested positive for pregnancy before taking the medication) or are currently breastfeeding; 15. Subjects whom the investigator considers unsuitable for participation in this clinical study due to any clinical or laboratory abnormalities or other reasons; 16. Those with routine urine test indicating urinary protein ≥2, and 24-hour urine protein quantification >1.0g;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Surufatinib + Toripalimab + mFOLFIRINOX

Drug: Surufatinib; Surufatinib: 200 mg orally once daily, continuous dosing, with each 14 days as one treatment cycle; Drug: Toripalimab; Toripalimab: 3 mg/kg per dose, intravenous infusion over 1 hour, on day 1, with each 14 days as one treatment cycle; Drug: mFOLFIRINOX; Oxaliplatin: 68 mg/m² intravenous infusion over 2 hours, on day 1; Irinotecan: 135 mg/m² intravenous infusion over more than 30-90 minutes, on day 1; Calcium folinate: 400 mg/m² intravenous infusion over 2 hours, on day 1; 5-FU: 2400 mg/m² continuous intravenous infusion over 46 hours; With each 14 days as one treatment cycle; Neoadjuvant treatment for up to 8 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
12-month Event Free Survival Rate	Event-free survival (EFS) is defined as the time from enrollment to the first occurrence of any of the following events, including (1) disease progression according to RECIST criteria, (2) undergoing R2 resection surgery, (3) disease recurrence after surgery, or (4) death from any cause. The 12-month EFS rate is defined as the proportion of patients among the total enrolled who have not experienced any of the above predefined events within 12 months from enrollment.	From enrollment to the end of observation at 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
R0 Resection Rate	The proportion of patients whose postoperative pathological evaluation shows no residual tumor cells at all surgical margins (R0) among all patients who underwent surgery after receiving neoadjuvant therapy.	From enrollment to the end of treatment for up to 16 weeks
Objective Response Rate	Refers to the proportion of patients whose tumors shrink by a certain amount and maintain it for a certain period of time, including cases of CR and PR. The objective response rate is evaluated using the RECIST 1.1. Subjects must have measurable tumor lesions at enrollment, and the efficacy evaluation criteria according to RECIST 1.1 are classified as complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD).	From enrollment to the end of treatment for up to 16 weeks
Disease Control Rate	Refers to the percentage of patients with complete response, partial response, and stable disease maintained for more than 4 weeks among those evaluable for efficacy.	From enrollment to the end of treatment for up to 16 weeks
Recurrence Free Survival	Recurrence-free survival (RFS) refers to the time interval from the date of surgery following neoadjuvant therapy to the recurrence of the tumor (including local/regional recurrence or distant metastasis) or death from any cause.	From the date of surgery at week 18 to the recurrence of the tumor or death for up to 96 weeks.
Overall Survival	Overall survival (OS) refers to the time from enrollment to the date of death from any cause.	From enrollment to the date of death from any cause for up to 96 weeks.
AEs	Collect adverse events (AEs) from enrollment to 30 days after the end of treatment, and grade the AEs according to CTCAE 5.0.	From enrollment to 30 days after the end of treatment at 16 weeks

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Estimated): March 31, 2026
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): January 31, 2029

Study Registration Dates

• First Submitted: February 11, 2026
• First Submitted That Met QC Criteria: March 9, 2026
• First Posted (Actual): March 13, 2026

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 9, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Resectable; Pancreatic cancer; Toripalimab; Surufatinib
• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Pancreatic Neoplasms; toripalimab; surufatinib
• Other Study ID Numbers: HMPL-012-SPRING-P108

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No