Peptide Nanovaccine (ONVAX-01) Plus Anti-PD-1 Antibody and Chemotherapy in Advanced Pancreatic Cancer

Inclusion criteria

• • Age between 18 and 75 years (inclusive).

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically confirmed, KRAS-mutated, unresectable metastatic pancreatic ductal adenocarcinoma (PDAC).
• Documented disease progression after at least one prior line of systemic therapy.
• Estimated life expectancy of ≥ 12 weeks.
• At least one measurable objective tumor lesion according to RECIST v1.1. The maximum diameter must be ≥ 1 cm by spiral CT, or ≥ 2 cm by standard CT or MRI; imaging must be performed within 28 days prior to enrollment.
• Adequate bone marrow and organ function, defined as follows (without the use of hematopoietic growth factors or blood transfusions within 7 days prior to testing):

• Hematology: Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L, platelet count ≥ 75 × 10^9/L, and hemoglobin ≥ 90 g/L.
• Hepatic: Total bilirubin ≤ 1.5 × upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN.
• Renal: Creatinine clearance ≥ 60 mL/min (calculated using the Cockcroft-Gault formula).
• Coagulation: International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN.
• Cardiac: Normal electrocardiogram (ECG) or abnormal ECG deemed clinically insignificant by the investigator.
• Urinalysis: Urine protein < 2+; if urine protein is ≥ 2+, a 24-hour urine protein quantification must be < 1.0 g.
• Participants of childbearing potential must agree to use highly effective contraceptive measures from study entry throughout the study period.
• Participants with active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection must have received at least 14 days of continuous antiviral therapy prior to the first study dose. HBV DNA titer must be ≤ 500 IU/mL (or 2500 copies/mL) and HCV RNA must be below the lower limit of detection. Participants must be willing to continue effective antiviral therapy during the study.

Exclusion criteria

• • Receipt of anti-tumor chemotherapy, radiotherapy, or immunotherapy within 2 weeks prior to the first dose of the study vaccine.

• History of other malignancies, except adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, non-muscle invasive bladder cancer (Ta and TIS), or other malignancies curatively treated at least 5 years prior to enrollment.
• Uncontrolled concomitant diseases, including but not limited to active bacterial or fungal infections, symptomatic congestive heart failure, unstable angina, or cardiac arrhythmias.
• Prior treatment with any antibody or drug targeting T-cell co-regulatory proteins (immune checkpoints), such as anti-PD-1, anti-PD-L1, anti-CTLA-4, anti-OX-40, anti-CD137, anti-TIM-3, or anti-LAG-3 antibodies.
• Human Immunodeficiency Virus (HIV) infection, or active uncontrolled HBV (HBV DNA ≥ 500 IU/mL) or HCV infection.
• Uncontrolled coronary artery disease, asthma, cerebrovascular disease, or any other medical conditions deemed unsuitable for enrollment by the investigator.
• Active autoimmune disease, primary or secondary immunodeficiency, or current treatment with immunosuppressive medications.
• Pregnant or lactating women.
• Receipt of any prophylactic vaccines for infectious diseases within 4 weeks prior to the first dose, or planned vaccination during the study up to 8 weeks after the last dose.
• History of severe allergic reactions to prior prophylactic vaccines.
• Known allergy or hypersensitivity to the investigational drugs or any of their excipients.
• History of substance abuse, or any clinical, psychological, or social factors that would preclude the administration of immunotherapy.
• Significant weight loss (≥ 10% of body weight) within 6 weeks prior to enrollment.
• Any other condition or uncertainty that, in the investigator's judgment, could compromise patient safety or compliance with the study protocol.