This is a randomized non-comparative, multicenter phase II study in patients with PD-L1 PD-L1 combined positive score (CPS) ≥5 advanced gastric cancer to evaluate the efficacy and safety of nivolumab and FOLFOX in combination with EXL01 as first-line treatment.
After signing the informed consent form, and upon confirmation of the patient's eligibility, patients will be randomized in a 2:1 ratio to either the nivolumab and FOLFOX plus EXL01 arm (experimental) or the nivolumab and FOLFOX arm (control). In both arms, treatment will be given until PD, unacceptable toxicity or for a maximum of 24 months (52 cycles).
Patients must have dated and signed an approved written informed consent form. This must be obtained before the performance of any protocol-related procedures that are not part of normal patient care.
Patients must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests and other requirements of the study,
Inoperable, advanced, or metastatic gastric cancer or gastroesophageal junction or distal esophageal carcinoma and histologically confirmed predominant adenocarcinoma,
Expression of PD-L1 with a combined positive score (PD-L1 CPS) ≥5, Note: information must be available at the time of inclusion, the examination will be performed locally in the center and secondarily confirmed centrally,
Known HER-2 positive status or unknown HER-2 status before inclusion,
Active brain metastases or known history of leptomeningeal carcinomatosis,
Ascites, which cannot be controlled with appropriate interventions,
Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast,
Parallel
Nivolumab
DrugNivolumab 240 mg IV; every 2 weeks
FOLFOX regimen
DrugOxaliplatin 85 mg/m², leucovorin 400 mg/m², bolus of 5-FU 400 mg/m², continuous 5-FU 2400/m² in 46 hours; every 2 weeks
EXL01
Biological/VaccineOrally 1 capsule/day, starting on day 1 of each FOLFOX/nivolumab treatment.
Objective response rate (ORR) at 4 months
ORR measured at 4 months post randomization in patients with PD-L1 CPS ≥5 advanced gastric cancer treated by first-line EXL01 plus nivolumab and FOLFOX. ORR at 4 months is defined as the number of patients with a CR or PR evaluated by RECIST v 1.1 criteria divided by the number of patients evaluable.
Overall survival (OS)
OS with nivolumab plus FOLFOX with or without EXL01. OS is defined as the time between the date of randomization and the date of death from any cause.
Progression-free survival (PFS)
PFS per RECIST v 1.1 and iRECIST of nivolumab plus FOLFOX with or without EXL01. PFS is defined as the time from randomization to the date of the first documented PD determined by the Investigator assessment by RECIST 1.1 or death due to any cause, whichever occurs first.
Assessment of safety profile
Safety of nivolumab plus FOLFOX with or without EXL01. Safety will be measured by the incidence of Adverse Events (AEs), Serious AEs (SAEs), deaths, laboratory abnormalities, and specific immune-related AEs (hepatitis, colitis, myositis, endocrinopathies).
Duration of response (DoR)
DoR with FOLFOX plus nivolumab with or without EXL01. DoR is defined as the time between the date of first documented response (complete response \[CR\] or partial response \[PR\]) to the date of the first disease progression, per RECIST 1.1 or death due to any cause, whichever occurs first. For patients who neither progress nor die, the duration of objective response will be censored at the same time they were censored for the primary definition of PFS.
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