Trial Title:
Personalized Neoantigen Cancer Vaccine for Patients with Solid Tumors
NCT ID:
NCT06614140
Condition:
Cancer
Solid Tumor, Adult
Conditions: Official terms:
Neoplasms
Poly ICLC
Conditions: Keywords:
neoantigen
vaccine
personalized
cancer
peptide
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Active, not recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Biological
Intervention name:
Personalized Neoantigen Peptide Vaccine with Poly-ICLC and Checkpoint Inhibitors
Description:
This intervention involves a personalized neoantigen peptide vaccine composed of peptides
containing tumor-specific mutations, such as SNVs, indels, and frameshift mutations.
Neoantigens are selected based on criteria that enhance expression and immunogenicity.
The vaccine is administered alongside Poly-ICLC, a TLR3 agonist, to enhance immune
activation. After the initial vaccine doses, checkpoint inhibitors (e.g., anti-PD-1 or
anti-PD-L1) are introduced once neoantigen-specific T-cell responses are detected,
preventing immune exhaustion and sustaining a strong immune response.
During the follow-up phase, both checkpoint inhibitors and Poly-ICLC are continued to
maintain immune activity and ensure a lasting anti-tumor effect.
Arm group label:
Personalized Neoantigen Peptide Vaccine with Poly-ICLC and Checkpoint Inhibitors
Summary:
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.
Detailed description:
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.
Criteria for eligibility:
Criteria:
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Vejthani Hospital
Address:
City:
Bangkok
Zip:
10240
Country:
Thailand
Start date:
November 24, 2022
Completion date:
August 15, 2025
Lead sponsor:
Agency:
Seqker Biosciences, Inc.
Agency class:
Industry
Source:
Seqker Biosciences, Inc.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06614140
