Efficacy and Safety of Serplulimab in Combination With Bevacizumab and FOLFIRINOX or NALIRIFOX as Second-Line Therapy in Patients With Metastatic Pancreatic Ductal Adenocarcinoma

NCT07733050 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: HLX10IIT343
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This is an investigator-initiated, open-label, single-arm, phase II trial evaluating the efficacy and safety of serplulimab (an anti-PD-1 monoclonal antibody) plus bevacizumab, combined with either FOLFIRINOX or NALIRIFOX chemotherapy, as second-line treatment for metastatic pancreatic ductal adenocarcinoma. The study will enrol up to 34 patients.

Conditions

Metastatic Pancreatic Ductal Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Overall Survival (OS)

  Overall survival is defined as the time from the date of first study drug administration to the date of death from any cause, assessed by the investigator per RECIST v1.1.

  From date of first dose to date of death from any cause, assessed up to approximately 24 months (or up to the end of study).

Secondary Outcomes (4)

• Progression-Free Survival (PFS)

  From date of first dose to date of first progression or death, assessed up to approximately 24 months.

• Objective Response Rate (ORR)

  From baseline to the end of treatment, assessed every 8 weeks during the study, up to approximately 24 months.

• Duration of Response (DOR)

  From first documented response to progression or death, assessed up to approximately 24 months.

• Incidence and Severity of Adverse Events (Safety)

  From signing of informed consent up to 30 days after the last dose of study treatment (or up to 90 days for SAEs related to serplulimab and irAEs), assessed up to approximately 27 months.

Study Arms (1)

Experimental group

EXPERIMENTAL

Patients receive serplulimab 200 mg intravenously (IV) on Day 1 of each 14-day cycle, combined with bevacizumab 6 mg/kg IV on Day 1, plus investigator's choice of either FOLFIRINOX or NALIRIFOX chemotherapy for 8 cycles (16 weeks) as second-line therapy. After the initial 16-week treatment period, patients who achieve disease control (complete response, partial response, or stable disease) based on imaging assessment proceed to maintenance therapy. Maintenance treatment consists of serplulimab 200 mg IV every 2 weeks, bevacizumab 5 mg/kg IV every 2 weeks, and oral S-1 (dose per local clinical practice). Treatment continues until disease progression, unacceptable toxicity, withdrawal of consent, or completion of the maximum 2-year serplulimab treatment duration.

Drug: Serplulimab and Bevacizumab injection; Drug: FOLFIRINOX/NALIRIFOX; Drug: S-1

Interventions

Serplulimab and Bevacizumab injection DRUG

Serplulimab：200 mg, intravenous infusion, Day 1 of each 14-day cycle Bevacizumab：6 mg/kg (second-line) or 5 mg/kg (maintenance), intravenous infusion, Day 1 of each 14-day cycle

Experimental group

FOLFIRINOX/NALIRIFOX DRUG

FOLFIRINOX:Oxaliplatin 68 mg/m² IV over 2h, Irinotecan 130 mg/m² IV over 30-90 min, Leucovorin 400 mg/m² IV over 2h, Fluorouracil 400 mg/m² IV bolus then 2400 mg/m² continuous IV over 46h, Day 1, every 14 days NALIRIFOX:Oxaliplatin 60 mg/m² IV over 2h, Liposomal Irinotecan 50 mg/m² IV over 90 min, Leucovorin 400 mg/m² IV over 30 min, Fluorouracil 2400 mg/m² continuous IV over 46h, Day 1, every 14 days

Experimental group

S-1 DRUG

Oral, dose per local clinical practice, during maintenance phase

Experimental group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Voluntary participation with signed written informed consent, good compliance, and willingness to adhere to follow-up visits.
• Age ≥ 18 years, male or female.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 and life expectancy ≥ 3 months.
• Histologically or cytologically confirmed locally advanced unresectable or metastatic pancreatic adenocarcinoma.
• Must have received prior first-line (1L) systemic therapy. Prior neoadjuvant or adjuvant chemotherapy is allowed if the last treatment was administered \> 6 months before disease recurrence/progression.
• No prior exposure to irinotecan or oxaliplatin.
• At least one measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
• Adequate major organ function, defined as follows:
• Hematology: Hemoglobin ≥ 90 g/L (no transfusion within 14 days); Absolute Neutrophil Count ≥ 1.5 × 10⁹/L; Platelets ≥ 75 × 10⁹/L.
• Biochemistry: Total bilirubin ≤ 1.5 × upper limit of normal (ULN); ALT and AST ≤ 3 × ULN (or ≤ 5 × ULN in the presence of liver metastases); Serum creatinine ≤ 1 × ULN with calculated creatinine clearance \> 50 mL/min (Cockcroft-Gault formula).
• Coagulation: International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN (or within therapeutic range for patients on stable anticoagulation).
• Thyroid: Normal TSH, or abnormal TSH with normal FT3/FT4 (e.g., controlled hypothyroidism).
• Cardiac: QTc interval (Fridericia's formula) ≤ 450 ms for males and ≤ 470 ms for females.
• \- Female participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to the first dose and agree to use effective contraception during the study and for 6 months after the last dose. Male participants with female partners of childbearing potential must agree to use effective contraception during the study and for 6 months after the last dose.

You may not qualify if:

• Prior treatment with anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibodies, or any other agents specifically targeting T-cell co-stimulation or immune checkpoint pathways.
• Prior treatment with bevacizumab or other anti-angiogenic agents. Radiological evidence of major vascular tumor invasion or high risk of fatal hemorrhage; active gastrointestinal bleeding, persistent bleeding disorders, or coagulopathy.
• Radiotherapy (except for palliative reasons), endocrine therapy, chemotherapy, immunotherapy, or molecular targeted therapy within 4 weeks prior to the first dose (bisphosphonates for bone metastases are allowed).
• Uncontrolled central nervous system (CNS) metastases (i.e., symptomatic or requiring corticosteroids or mannitol for symptom control).
• Clinically significant or uncontrolled cardiac disease within 6 months prior to the first dose, including congestive heart failure, angina pectoris, myocardial infarction, or ventricular arrhythmias.
• Other active malignancy within 5 years prior to the first dose, except for adequately treated basal cell carcinoma of the skin or cervical carcinoma in situ.
• Active autoimmune disease requiring systemic treatment within 2 years prior to the first dose. Exceptions: vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune thyroiditis requiring only hormone replacement therapy.
• History of immediate hypersensitivity reactions, eczema, or asthma not controlled by topical corticosteroids.
• History of drug-induced interstitial lung disease (ILD), pneumonitis, obstructive pulmonary disease severely affecting lung function, or symptomatic bronchospasm.
• Severe infection (\> CTCAE Grade 2) requiring antibiotic therapy within 14 days prior to the first dose (e.g., severe pneumonia, bacteremia, infectious complications requiring hospitalization).
• Receipt of live-attenuated vaccine within 4 weeks prior to the first dose, or planned vaccination during the study period.
• Known human immunodeficiency virus (HIV) infection, history of allogeneic organ transplantation, or allogeneic hematopoietic stem cell transplantation.
• History of allergy or hypersensitivity to any component or excipient of the investigational drugs.
• Any other condition deemed by the investigator to be unsuitable for participation in the study.

Sponsors & Collaborators

• Shanghai General Hospital, China: lead

Study Sites (1)

Shanghai General Hospital

Shanghai, Shanghai Municipality, 200080, China

Location

MeSH Terms

Interventions

Bevacizumab; folfirinox; S 1 (combination)

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Fan wang

CONTACT

13564260428; fairywong04285@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Chief Physician

Study Record Dates

• First Submitted: July 23, 2026
• First Posted: July 29, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): August 1, 2027
• Study Completion (Estimated): August 1, 2028
• Last Updated: July 29, 2026

Record last verified: 2026-07

Locations

CN (1)