The primary hypothesis is that cancer vaccine can convert non-immunogenic gastric cancer into immunogenic phenotype susceptible to PD1 inhibition. This would lead to an improved radiological response rate and favorable immune contexture for immune checkpoint blockade
Primary Objectives 1. Safety cohorts: To evaluate the safety of OTSGC-A24 and nivolumab (+ ipilimumab) in patients with refractory gastric cancer. 2. Arm A: To determine the objective response rate of OTSGC-A24 and nivolumab in advanced gastric cancer. 3. Arm B: To determine the objective response rate of OTSGC-A24 and nivolumab + ipilimumab in advanced gastric cancer. Secondary Objectives 1. To compare the difference in objective response rates between Arm A and Arm B 2. To compare the tumoral immune contexture and PDL-1 expression before treatment, after OTSGC-A24, and after nivolumab (+ ipilimumab) in combination with OTSGC-A24. 3. To determine the serum cytotoxic T-cell response using enzyme-linked immunospot assay (ELISPOT) in PBMC. 4. To determine the progression-free survival (PFS) and overall survival (OS) of Arm A and Arm B. 5. To evaluate the effect of OTSGC-A24 and nivolumab + ipilimumab on clinical and immune PD markers. 6. Evaluate the effects of treatment on peripheral T-cell phenotypic profiles with epitope-specificities by coupling mass cytometric analyses with highly-multiplexed peptide-MHC tetramer staining technology. 7. Identify potential biomarkers for treatment response and mechanisms of secondary resistance by studying gene expression profiles and phenotypic/functional markers of tumour and infiltrating immune cells. End Points - Efficacy The endpoints for efficacy are: * Induction of specific CTL response after vaccination * Response rate * Progression-free survival * Overall survival End Points - Safety The endpoints for safety are: • overall adverse events observed, treatment-related adverse events, and category (eg percentage of patients with any-grade treatment-related adverse events and grade 3-4 treatment-related adverse events).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
OTSGC-A24 is administered as a subcutaneous (under the skin) injection. Nivolumab and ipilimumab are administered by intravenous (IV) infusion, meaning the drug is given through a catheter in a vein. A pump will be used to ensure the correct amount of medicine is given through the catheter. The nivolumab and ipilimumab infusions each take about 30 minutes. There will be a break of about 30 minutes in between the nivolumab and ipilimumab infusions (if given on the same day). OTSGC-A24 and nivolumab are administered every 2 weeks, while ipilimumab is administered every 6 weeks.
OTSGC-A24 is administered as a subcutaneous (under the skin) injection. Nivolumab and ipilimumab are administered by intravenous (IV) infusion, meaning the drug is given through a catheter in a vein. A pump will be used to ensure the correct amount of medicine is given through the catheter. The nivolumab and ipilimumab infusions each take about 30 minutes. There will be a break of about 30 minutes in between the nivolumab and ipilimumab infusions (if given on the same day). OTSGC-A24 and nivolumab are administered every 2 weeks, while ipilimumab is administered every 6 weeks.
National University Hospital
Singapore, Singapore
RECRUITINGAdverse Event and Adverse Drug Reaction
Time frame: 3 years
Response Rate
Time frame: 3 years
Rate of induction of specific CTL response
Time frame: 3 years
Progression-free Survival
Time frame: 3 years
Overall Survival
Time frame: 3 years
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OTSGC-A24 is administered as a subcutaneous (under the skin) injection. Nivolumab and ipilimumab are administered by intravenous (IV) infusion, meaning the drug is given through a catheter in a vein. A pump will be used to ensure the correct amount of medicine is given through the catheter. The nivolumab and ipilimumab infusions each take about 30 minutes. There will be a break of about 30 minutes in between the nivolumab and ipilimumab infusions (if given on the same day). OTSGC-A24 and nivolumab are administered every 2 weeks, while ipilimumab is administered every 6 weeks.