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

An Exploratory Clinical Study of Peptide Nanovaccine (ONVAX-01) and Anti-PD-1 Antibody Combined With Chemotherapy for the Treatment of Advanced Pancreatic Cancer

The goal of this clinical trial is to evaluate the safety and preliminary effectiveness of a new combination therapy in patients with advanced pancreatic cancer.

The main questions it aims to answer are:

1. Is the combination of the peptide nanovaccine (ONVAX-01), an anti-PD-1 antibody, and chemotherapy safe and well-tolerated?
2. Does this combination treatment help shrink tumors or stop the progression of advanced pancreatic cancer?

Participants will be asked to:

1. Receive doses of the peptide nanovaccine (ONVAX-01).
2. Receive intravenous infusions of an anti-PD-1 antibody and standard chemotherapy.
3. Undergo regular physical exams, blood tests, and imaging scans (such as CT or MRI) to monitor their health and the tumor's response to the treatment.

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.