Digestive System Neoplasms
Conditions
Keywords
iNeo-Vac-R01, Personalized mRNA Vaccine, Neoantigen, Digestive System Neoplasms
Brief summary
The purpose of this study is to assess the safety, feasibility, and efficacy of personalized mRNA vaccine iNeo-Vac-R01 alone in subjects with advanced digestive system neoplasms.
Detailed description
This is a multi-part single-center, open-label, single-arm clinical study of personalized mRNA vaccine iNeo-Vac-R01 monotherapy in subjects with advanced digestive system neoplasms. The study will include a dose escalation phase and dose expansion phase. The traditional 3+3 design will be used in dose escalation.
Interventions
BIOLOGICALiNeo-Vac-R01
Personalized mRNA vaccine encoding neoantigen, IH injection
Sponsors
Hangzhou Neoantigen Therapeutics Co., Ltd.
Sir Run Run Shaw Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female, \>/= 18 years old and \</= 75 years old, with the ability to understand and provide signed and witnessed informed consent, and agree and are able to comply with protocol requirements. 2. Subjects must have one of the histologically- or cytologically-confirmed advanced (locally advanced or metastatic) digestive system neoplasms, have measurable disease at study entry defined by RECIST v1.1. Subjects must have tumor progression after standard treatment or are intolerant or are unwilling to receive standard treatment. The toxic effects of previous anti-tumor treatments have returned to \</= grade 1 defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 or to the level specified by the inclusion/
Exclusion criteria
. 3. Expected survival \>/= 6 months. 4. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 \ 2. 5. Sufficient tumor tissue samples can be obtained from subjects for genetic analysis, with at least 2 puncture tissues with a tumor purity of ≥ 50% required for puncture samples and at least 0.5cm of tissue required for surgical samples. Alternatively, the original gene sequencing data required for tumor neoantigen analysis can be provided, including full exon sequencing data of tumor tissue, transcriptome sequencing data, and full exon sequencing data of peripheral blood. 6. Echocardiographic evaluation: left ventricular ejection fraction (LVEF) \>/= 50%. 7. The organ function level must meet the following requirements: absolute neutrophil count (ANC) \>/= 1.5 × 10\^9/L, platelet count (PLT) \>/= 80 × 10\^9/L, hemoglobin (Hb) \>/= 90 g/L; serum total bilirubin (TBIL) \</= 1.5 × ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \</= 2.5 × ULN (if there is liver metastasis, TBIL \</= 3 × ULN, AST, ALT \</= 5 ×ULN are allowed), serum albumin \>/= 28g/L, serum creatinine \</= 1.5 × BUN, Glomerular filtration rate \>/= 50mL/min, prothrombin time (PT) and activated partial thromboplastin time (APTT) and international standardized ratio (INR) \</= 1.5 × ULN (without anticoagulant therapy) . 8. For women of childbearing potential: having a negative serum or urine pregnancy test within 7 days prior to study initiation, agreement to remain abstinent or use contraceptive measures during the treatment period. 9. For men: agreement to remain abstinent or use contraceptive measures during the treatment period.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse Events (AEs) [safety and tolerability] | 21 days after last iNeo-Vac-R01 dose | — |
| Proportion of Subjects Receiving iNeo-Vac-R01 Injection Treatment to Enrolled Subjects [feasibility] | 21 days after last iNeo-Vac-R01 dose | — |
| Dose-limiting Toxicity (DLT) | 28 days (+/-3 days) after first iNeo-Vac-R01 dose | Level 3 or 4 AEs related to iNeo-Vac-R01 injection. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | 3 years after first dose of iNeo-Vac-R01 | DOR is defined as time from first PR or CR until either disease progression or death (whichever is sooner). |
| Part A and Part B: Progression Free Survival (PFS) | 3 years after first dose of iNeo-Vac-R01 | PFS is defined as time between the date of first dose of iNeo-Vac-R01 and the date of either disease progression or death (whichever is sooner). |
| Overall Survival (OS) | 3 years after first dose of iNeo-Vac-R01 | OS is defined as time between the date of the first dose of iNeo-Vac-R01 and the date of death due to any cause. |
| T Cell Subsets [immunogenicity] | 12 months after first dose of iNeo-Vac-R01 | Detect the proportion of different T cell subsets in T cells by flow cytometry. |
| Cytokines Level [immunogenicity] | 6 months after first dose of iNeo-Vac-R01 | Record the changes of IL-2, IL-6, IL-8, IL-10, IL-12, and TNF-α in peripheral blood before and after treatment. |
| Neoantigen-specific T Cell Response [immunogenicity] | 12 months after first dose of iNeo-Vac-R01 | Detect the level of specific TNF-γ in peripheral blood of subjects by ELISpot in order to measure the neoantigen-specific T cell response of subjects. |
| Objective Response Rate (ORR) | 3 years after first dose of iNeo-Vac-R01 | ORR is defined as proportion of subjects with complete response (CR) and partial response (PR) to all subjects based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. |
| Disease Control Rate (DCR) | 3 years after first dose of iNeo-Vac-R01 | DCR is defined as proportion of subjects with reduced or stable neoplasms that have been maintained for a certain period of time, including the proportion of subjects with CR, PR, and stable disease (SD). |
Countries
China
Contacts
Primary ContactXiujun Cai, MD
Outcome results
None listed