This trial is an investigator-initiated, single-center, open-label, single-arm exploratory study of mRNA neoantigen tumor vaccine in the treatment of advanced gastric cancer, esophageal cancer, and liver cancer, including two phases: dose escalation and dose expansion. To evaluate the safety and tolerability of neoantigen tumor vaccine in subjects with advanced gastric cancer, esophageal cancer and liver cancer by conducting dose escalation trial in subjects diagnosed with advanced gastric cancer, esophageal cancer and liver cancer, and preliminarily evaluate the efficacy of neoantigen tumor vaccine in subjects with advanced gastric cancer, esophageal cancer and liver cancer. According to the characteristics of safety and efficacy data in the dose escalation phase, the dose expansion is performed at the intended clinical dose based on the investigator's judgment, and the treatment is performed in combination with PD-1/L1 to further evaluate the efficacy and safety profile of neoantigen tumor vaccine at a specific dose. Both the dose escalation phase and dose expansion phase include a screening period (Week -4 \~ Week -2), a baseline period (Week -1 \~ Day -1), a treatment period (Day 1 \~ Week 8 or 16), and a follow-up period. Subjects who signed and provided the formal informed consent entered the screening period. The treatment period included the initial treatment period (Day 1 \~ Week 8) and the enhanced treatment period (Week 12 \~ Week 16). The investigator determined whether to enter the enhanced treatment period based on the comprehensive judgment of the subject's efficacy, safety, compliance and other factors from Week 8 to Week 12. The dose escalation phase follows standard 3+3 design. 12-18 subjects are expected to be enrolled at 3 given dose level. The investigator will choose the optimal clinical dose for dose expansion, which can be one dose group or multiple dose groups. PD-1/L1 drugs are used in parallel to further confirm the efficacy and safety of neoantigen tumor vaccine, with about 18 subjects. The usage and dosage of PD-1/L1 should aligned with the package insert.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
In dose escalation phase, subjects will receive neoantigen tumor vaccine only. In dose expansion phase, subjects will receive neoantigen tumor vaccine combination with PD-1/L1.
PLA General Hospital
Beijing, Beijing Municipality, China
RECRUITINGIncidence and degree of Adverse Events and Serious Adverse Events [Safety]
Incidence and degree of participants with adverse events(CTCAE 5.0), abnormal laboratory tests (hematology, blood biochemistry, coagulation and urinalysis), abnormal ECG, abnormal echocardiography, abnormal vital signs and abnormal physical examination
Time frame: Up to 100 weeks
Objective Response Rate (ORR)
Objective Response Rate (ORR): The proportion of patients with complete response(CR) or partial response(PR) as measured by RECIST 1.1 criteria
Time frame: Up to 100 weeks
The establishment of recommended dose for further studies
To determine the recommended dosage for pivotal study
Time frame: Up to 16 weeks
Progression Free Survival (PFS)
the time (in days) from the first dose of study treatment to the occurrence of disease progression; for subjects who die due to other causes before disease progression, the time (in days) from the date of entry into the treatment period to the date of death will be calculated, whichever occurs first. Response determination will be performed according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1
Time frame: Up to 100 weeks
The concentration of Serum cytokine
IL-1β, IL-2, IL-6, IL-8, IL-10, TNF-α from time zero to time of last dose concentration
Time frame: Up to 16 weeks
The concentration of Lymphocyte
CD3+ 、CD3+∕CD4+ %、CD3+∕CD8+ %、CD4∕CD8 、CD3-∕CD19+ % from time zero to time of last dose concentration
Time frame: Up to 16 weeks
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