Clinical Trial of Repeated Intraperitoneal Administration of GAIA-102 in Patients With Advanced Gastrointestinal Cancer (Gastric Cancer / Pancreatic Cancer) of Microsatellite Stable (MSS) With Malignant Ascites (Phase I / II Investigator-initiated Clinical Trial) (GAIA-102-PD Clinical Trial)
Phase I Part : Confirm the safety of GAIA-102 as a monotherapy or GAIA-102 and pembrolizumab in combination for advanced gastrointestinal cancer of microsatellite stable with malignant ascites, and determine the recommended number of doses for Phase II part. Phase II Part(Gastric Cancer):Comparative Study Research the efficacy and safety of as a monotherapy or GAIA-102 and pembrolizumab for advanced gastrointestinal cancer of microsatellite stable with malignant ascites at the recommended dose of GAIA-102 decided in the Phase I part. Phase II Part (Pancreatic Cancer): Comparative Study Including a Run-in Cohort Research the efficacy and safety of a combination regimen of GAIA-102 and pembrolizumab added to existing chemotherapy (standard of care) for microsatellite stable advanced pancreatic cancer with malignant ascites at the recommended dosing frequency of GAIA-102 decided in the Phase I part.
• Unresectable or advanced recurrent gastric cancer with evident peritoneal dissemination on imaging, or with malignant ascites, as well as unresectable or advanced recurrent pancreatic cancer.
• Phase I:
⁃ Patients with gastric cancer who have received 3 or more prior chemotherapy regimens and are refractory or intolerant to these therapies, and patients with pancreatic cancer who have received 2 or more prior chemotherapy regimens and are refractory or intolerant to these therapies.
⁃ Phase II:
⁃ Patients with gastric cancer who have received 2 or more prior chemotherapy regimens, including at least 1 regimen containing an immune checkpoint inhibitor, and are refractory or intolerant to these therapies, and patients with pancreatic cancer who have received 1 or more prior chemotherapy regimens, including at least 1 regimen containing gemcitabine, and are refractory or intolerant to these therapies.
⁃ Only patients with HER2-negative gastric cancer are eligible.
• Abdominal port placement is possible
• Phase I:
⁃ No medical history of serious adverse reactions or allergic reactions to pembrolizumab (only for patients in the pembrolizumab combination cohort)
⁃ PhaseⅡ(gastric cancer):
⁃ No medical history of serious adverse reactions or allergic reactions to pembrolizumab or trifluridine/tipiracil hydrochloride (FTD/TPI) ,or to any components of these agents.
⁃ PhaseⅡ(pancreatic cancer):
⁃ No medical history of serious adverse reactions or allergic reactions to pembrolizumab, irinotecan hydrochloride hydrate, fluorouracil, or calcium levofolinate hydrate ,or to any components of these agents.
• Diagnosed gastric adenocarcinoma or pancreatic cancer with by histological or cytological examination
• The patient has been confirmed to be negative (not MSS = MSI-high) by microsatellite instability (MSI) testing, or proficient mismatch repair (pMMR) by mismatch repair protein immunohistochemistry testing
• The Eastern Cooperative Oncology Group (ECOG) Performance Status(PS) at the time of informed consent meets the following conditions.
⁃ Phase I ：0-2, Phase II ：0-1
• Patient aged 20years or older
• Adequate major organs (bone marrow, heart, lungs, liver, kidneys, etc.) function:
⁃ Neutrophil ≧1,500/mm3, hemoglobin ≧8.0 g/dL, Platelet ≧75,000/mm3, PT-INR≦ 1.5 , AST, ALT≦ 3 times the upper limit of reference value, T-Bil≦ 2 times the upper limit of reference value (T-Bil ≦ 3.0mg/dL , when drainage for obstructive jaundice), eGFR ≧30mL/min/1.73m2
• Expected to survive for 3 months or more at the enrollment
• Written informed consent