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

Official title

Efficacy and Safety of Serplulimab in Combination With Bevacizumab and FOLFIRINOX or NALIRIFOX as Second-Line Therapy in Patients With Metastatic Pancreatic Ductal Adenocarcinoma: An Open-Label, Single-Arm, Phase II Study

Overview

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.

Interventions

• Drug Serplulimab and Bevacizumab injection
  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
• Drug FOLFIRINOX/NALIRIFOX
  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
• Drug S-1
  Oral, dose per local clinical practice, during maintenance phase

Primary outcome measures

• Overall Survival (OS) [Time frame: 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 outcome measures (4)

• Progression-Free Survival (PFS) [Time frame: From date of first dose to date of first progression or death, assessed up to approximately 24 months.]
• Objective Response Rate (ORR) [Time frame: From baseline to the end of treatment, assessed every 8 weeks during the study, up to approximately 24 months.]
• Duration of Response (DOR) [Time frame: From first documented response to progression or death, assessed up to approximately 24 months.]
• Incidence and Severity of Adverse Events (Safety) [Time frame: 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.]

Eligibility criteria

Inclusion criteria

• 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.

Exclusion criteria

• 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.
• Persistent toxicities from prior therapy ≥ Grade 1 (per NCI-CTCAE v5.0), including Grade 1 peripheral neuropathy. Exceptions: alopecia or conditions deemed not exclusionary by the investigator (with clear documentation).
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shanghai General Hospital — Shanghai

Identifiers

NCT: NCT07733050 · HLX10IIT343

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗