Gastrointestinal Tumors, Personalized Neoantigen Vaccine in Combination With Anti-PD-1 Inhibitors in Standard Therapy-Failed and Adjuvant Therapy
Conditions
Keywords
neoantigen, p-MHC-TCR, CRC, mRNA, machine learning
Brief summary
Evaluating the efficacy and safety of Neoantigen Personalized Cancer Vaccine deepGeneAI-001 in combination with Sintilimab in the treatment of Gastrointestinal Solid Tumors
Detailed description
This is a single-center, open, single-arm exploratory clinical study to evaluate the efficacy and safety of Neoantigen Personalized Cancer Vaccine deepGeneAI-001 in combination with Sintilimab in the treatment of Gastrointestinal Solid Tumors, and to provide more clinical treatment options for gastrointestinal cancer patients.
Interventions
BIOLOGICALNeoantigen Personalized Cancer Vaccine
Cohort 1: subjects will receive neoantigen tumor vaccine combination with Sintilimab. Cohort 2: subjects will receive neoantigen tumor vaccine combination with Sintilimab and chemotherapy .
Sponsors
deepGeneAI
Bio-X Institutes, Shanghai Jiao Tong University
Ruijin Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Voluntarily signs the informed consent form, and has good compliance. 2. Male or female, aged 18 years or older. 3. Patients with advanced gastrointestinal tumors: histologically and/or cytologically confirmed recurrent or metastatic gastrointestinal solid tumors not amenable to surgical or local curative treatment, with at least one measurable lesion as defined by RECIST v1.1. Eligible patients must have experienced disease progression following standard antitumor therapy or be unable or unwilling to receive standard treatment. Patients with resectable gastrointestinal solid tumors for adjuvant treatment: tumors must be confirmed as completely resected (R0 or R1) by postoperative histopathology, with no prior neoadjuvant therapy, and assessed as fully resectable by imaging. 4. Neoantigen load requirement: at least 10 predicted neoantigen epitopes. 5. The subject must have a tumor lesion suitable for repeated sampling for sequencing and immune testing. Fresh or archived tumor tissue is required, preferably from surgical or core needle biopsy (CNB) samples, including both tumor and 2-3 soybean-sized peritumoral tissues. Paraffin blocks or at least 10-20 unstained tumor tissue sections (4-6 μm thick) with tumor content \>20% are acceptable. If the subject cannot provide suitable samples but meets other inclusion/
Exclusion criteria
, the investigator may still consider enrollment. 6. ECOG performance status of 0 or 1. 7. Life expectancy of at least 6 months. 8. Adequate organ and hematologic function, with no severe dysfunction of the heart, lungs, liver, kidneys, or immune system, based on the following laboratory values: 1). Hematology: ANC ≥ 1.5 × 10⁹/L, WBC ≥ 3 × 10⁹/L, PLT ≥ 100 × 10⁹/L, HGB ≥ 90 g/L. Within one week before screening, the subject must not have received blood or platelet transfusions, G-CSF, or erythropoietin (EPO); 2). Renal function: Serum creatinine ≤ 1.5 × ULN or creatinine clearance ≥ 50 mL/min (calculated using the Cockcroft-Gault formula); 3). Liver function: AST and ALT ≤ 3 × ULN (≤ 5 × ULN for patients with liver cancer or liver metastases); TBIL ≤ 1.5 × ULN (patients with Gilbert's syndrome: TBIL \< 3 × ULN); 4). Coagulation: INR ≤ 2 × ULN or APTT ≤ 1.5 × ULN (except for patients on anticoagulants); 5). Endocrine function: TSH within normal limits. Note: If baseline TSH is outside the normal range but free T3 and free T4 are within normal limits, the subject is still eligible. 9\. Agrees to provide peripheral blood samples and, optionally, fresh peritumoral tissue for sequencing. 10\. Male subjects with reproductive potential and female subjects of childbearing potential agree to use effective contraception from the time of informed consent until 6 months after the last dose of investigational drug. * Women of childbearing potential include premenopausal women and those within 2 years post-menopause. * A negative serum pregnancy test is required within 7 days before the first dose of the investigational product.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Adverse events as graded by CTCAE v5.0 | Up to 2.5 years |
| Serious adverse events as graded by CTCAE v5.0 | Up to 2.5 years |
| Immunogenicity of a personalized cancer vaccine as measured by interferon-γ secreting T lymphocytes in peripheral blood mononuclear cells (PBMCs) using ELISpot | Up to 2.5 years |
Secondary
| Measure | Time frame |
|---|---|
| Cohort 1: Progression Free Survival (PFS) as assessed by RECIST 1.1 | Up to 2.5 years |
| Cohort 1: Overall Survival (OS) | Up to 2.5 years |
| Cohort 1: Objective Response Rate (ORR) by RECIST 1.1 | Up to 2.5 years |
| Cohort 2: 18-month Overall Survival (OS) rate | Up to 2.5 years |
| Cohort 2: 18-month Recurrence-free survival (RFS) rate | Up to 2.5 years |
| Cohort 1: Duration of Response (DOR) | Up to 2.5 years |
| Cohort 1: Disease Control Rate (DCR) | Up to 2.5 years |
Countries
China
Contacts
Primary ContactHao Li, MD, PhD
Outcome results
None listed