This clinical trial aims to evaluate the safety, immunogenicity, and preliminary efficacy of a personalized neoantigen peptide vaccine in patients with advanced cancer or at high risk of recurrence. The study is designed for patients whose tumors have specific mutations identifiable through genomic sequencing. These mutations, known as neoantigens, are unique to each patient's cancer and serve as the target for the personalized vaccine.

Eligible patients will undergo genomic analysis, including whole exome sequencing and RNA sequencing, to identify these neoantigens. A custom peptide vaccine will then be produced and formulated to target these neoantigens. The trial consists of a preparation phase, a treatment phase with priming and booster vaccinations, and a follow-up/maintenance period of one year. The study will assess immune responses, clinical efficacy, and potential toxicities. By leveraging the immune system's ability to recognize and attack cancer cells, this vaccine aims to provide a new treatment option for patients with limited alternatives.

This Phase Ib/II, open-label, single-center study investigates the safety, immunogenicity, and preliminary efficacy of a personalized neoantigen peptide vaccine in patients with advanced cancer or high risk of recurrence. The trial aims to enroll 15-35 eligible patients and is divided into three phases: preparation, treatment, and follow-up.

Preparation Phase: Patients undergo genomic analysis using whole exome sequencing and RNA sequencing to identify specific neoantigens from their tumor tissues. Based on these findings, a personalized neoantigen peptide vaccine is produced and formulated. Poly-ICLC, an immune adjuvant, is administered intramuscularly twice weekly for four weeks prior to the first vaccine dose to enhance immune readiness.

Treatment Phase: The neoantigen peptide vaccine is administered alongside Poly-ICLC on days 1, 4, 8, 15, and 22. A checkpoint inhibitor (e.g., anti-PD-1 or anti-PD-L1) will be introduced once neoantigen-specific T cell responses are detected, to prevent immune exhaustion and sustain the immune response. Booster injections of the neoantigen vaccine are scheduled for weeks 12 and 20. Immune responses and adverse events will be closely monitored throughout this phase.

Follow-up Phase: During the follow-up phase, checkpoint inhibitors (administered per standard regimen) and Poly-ICLC (administered twice monthly) will be continued to maintain immune activity and ensure a lasting anti-tumor response. Safety, immune activity, and clinical outcomes will be closely monitored over a one-year period.

The primary endpoints include safety and immunogenicity, measured by adverse event monitoring and T-cell activation assays. Secondary endpoints will assess clinical efficacy, including tumor response rates, progression-free survival, and overall survival. Exploratory endpoints will involve biomarker analysis and immune profiling to correlate clinical outcomes with specific immune responses.

This study aims to validate the hypothesis that personalized neoantigen peptide vaccines, in combination with immune adjuvants and checkpoint inhibitors, can elicit strong immune responses and improve clinical outcomes in patients with advanced or high-risk recurrent cancers, especially where standard therapies have failed.

Inclusion Criteria:

Cancer patients will be selected from those receiving treatment at the Cancer Center, Vejthani Hospital. All participants must meet the following criteria:

1. Cancer patients must be aged 18 years or older.

2. Patients must provide informed consent and voluntarily agree to participate in the study.

3. Patients must have an estimated life expectancy of at least 6 months.

4. Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 and normal functioning of internal organs.

5. Patients must have been diagnosed with cancer based on clinical presentation and confirmed by pathological evidence, including diagnostic imaging.

6. Specific criteria for the cancer type under study:

   • Advanced-stage cancer: No available standard treatment, resistant to standard therapies, and/or the patient is ineligible or refuses standard treatments.
   • Early-stage cancer with high recurrence risk: Even after surgery and/or radiation therapy and completion of standard treatment, the cancer has a high risk of recurrence, and there is no clear adjuvant treatment available.

7. Patients must have tumor tissue suitable for analysis and production of neoantigen peptides.

8. For advanced-stage cancer (not in the adjuvant setting), patients must have radiologic evidence that can be used to assess response according to mRECIST1.1 criteria for solid tumors.

9. Patients must have normal liver, kidney, and laboratory function, as indicated by the following criteria:

   • Lymphocyte count ≥ 800 cells/µL
   • Neutrophil count ≥ 1,500 cells/µL
   • Platelet count ≥ 150,000 cells/µL
   • AST ≤ 2.5 times the upper limit of normal (ULN)
   • ALT ≤ 2.5 times the ULN
   • Total bilirubin ≤ 1.5 times the ULN
   • Serum creatinine ≤ 1.5 times the ULN

10. Patients must agree to avoid pregnancy or causing pregnancy, according to the following:

    • Female patients not of childbearing potential, defined as those who have had a hysterectomy and/or bilateral oophorectomy, have experienced menopause for more than 12 months, or are aged over 60.
    • Female patients of childbearing potential must have a negative pregnancy test during the preparation phase and before receiving the first dose of the vaccine. They must also agree to use effective contraception from the preparation phase until 120 days after the last treatment.
    • Male patients must agree to use effective contraception from the preparation phase until 180 days after the last treatment.

Exclusion Criteria:

Cancer patients will not be eligible to participate in the study if they meet any of the following conditions:

1. Patients with a known history of allergy to peptide vaccines.

2. Patients with a history of autoimmune disease.

3. Patients who have received chemotherapy or radiation therapy less than 4 weeks prior to enrollment or as determined by the physician. This also includes patients with unresolved side effects from previous treatment graded ≥2 (CTCAE v4.0).

4. Patients with cancer that has metastasized to the brain or central nervous system, unless they have been treated and the metastases are controlled, and have been off steroids for at least 4 weeks.

5. Patients with a history of another malignancy within the past 2 years, except for locally treated basal cell or squamous cell skin cancer.

6. Patients with a history of Human Immunodeficiency Virus (HIV) infection.

7. Patients with a history of Hepatitis B or C infection. For those without prior history, screening will be conducted. Patients who test positive for Hepatitis B (HBsAg) or Hepatitis C (HCV) will be excluded unless:

   • Hepatitis B is controlled with antiviral treatment, as evidenced by an undetectable viral load.
   • Hepatitis C has been treated and the viral load is undetectable.

8. Patients with symptomatic or uncontrolled heart disease, including unstable angina, acute myocardial infarction, heart failure (New York Heart Association Class III or IV), or arrhythmias requiring treatment.

   • Patients with pacemakers may be eligible if their heart rhythm has been stable for at least one month before receiving the neoantigen peptide vaccine.

9. Patients who have received live attenuated or killed vaccines within 28 days prior to the first dose of the neoantigen peptide vaccine.

10. Patients receiving immunosuppressive drugs or corticosteroids at a dose of more than 10 mg of prednisolone (except for inhaled or intranasal corticosteroids) within the last 4 weeks before enrollment.

11. Patients with underlying medical conditions that may interfere with the efficacy or safety of the peptide vaccine.

12. Pregnant or breastfeeding patients.