GAIA-102 Intraperitoneal Administration in Patients With Advanced Gastrointestinal Cancer of Microsatellite Stable With Malignant Ascites

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.

Study Overview

• Status: Recruiting
• Conditions: Gastric Cancer; Pancreatic Cancer
• Intervention / Treatment: Biological: GAIA-102; Biological: GAIA-102; Drug: Pembrolizumab; Drug: Pembrolizumab; Drug: Trifluridine/tipiracil hydrochloride (FTD/TPI); Drug: Irinotecan hydrochloride hydrate; Drug: Calcium levofolinate hydrate; Drug: Fluorouracil

• Study Type: Interventional
• Enrollment (Estimated): 176
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Eiji Oki; Phone Number: +81-92-642-5479; Email: oki.eiji.857@m.kyushu-u.ac.jp

Study Locations

• Japan
  • Fukuoka
    • Fukuoka, Fukuoka, Japan, 812-8582
      • Recruiting
      • Kyushu University Hospital
      • Contact: Eiji Oki; Phone Number: +81-92-642-5479; Email: oki.eiji.857@m.kyushu-u.ac.jp

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• Untreated cranial metastases.
• Diagnosed with meningeal carcinomatosis
• Received allogeneic hematopoietic stem cell transplantation
• Participated in other clinical trials / clinical trials within 30 days prior to obtaining written consent and used or had used the investigational product or investigational equipment.
• Existence or suspected active autoimmune disease
• Continued systemic immunosuppressive therapy with corticosteroids in excess of 10 mg / day in terms of prednisolone or other immunosuppressants within 14 days prior to investigational product administration
• Symptomatic interstitial pneumonia, or even if it is not symptomatic, it may interfere with diagnostic imaging in detecting new pneumonitis caused by the investigational product used in the clinical trial.
• Have active double cancer and need treatment for the double cancer
• Requires treatment as shown in "Unacceptable Combination / Supportive Therapy" during the clinical trial period
• Have a medical history of severe hypersensitivity to immune checkpoint inhibitors or immune-related adverse events requiring treatment
• Have one of the following complications Complication of cerebrovascular disorder with symptoms or history within 6 months before the enrollment, Active gastrointestinal perforation, fistula, diverticulitis, Symptomatic congestive heart failure, Bleeding tendency, Presence of blood clots that may cause embolism on the image, Unhealed fractures (excluding compression fractures associated with osteoporosis) or severe wounds requiring medical treatment, Uncontrollable digestive ulcer, Active infectious diseases requiring intravenous administration of antibiotics, antifungal agents or antiviral agents, HIV antibody positive
• At the time of the enrollment, the period from the following prior treatment or the end of treatment has not passed.

Surgery (including exploratory laparotomy / examination laparoscope): 2 weeks, Palliative radiotherapy: 1 week, Thoracic drainage: 1 week, Pretreatment antineoplastic (from the last administration): 3 weeks, Biopsy with incision, thoracic biopsy, treatment for trauma (excluding patients without wound healing), etc : 2 weeks

• Scheduled thoracotomy or abdominal surgery during the clinical trial period
• It is judged that it is difficult to enroll in this study due to clinically significant mental illness.
• Pregnant women, lactating women, women who are currently pregnant, or have no intention of contraception for 4 months after consent is obtained.
• Allergic to antibiotics and foreign animal-derived ingredients (pig and mouse)
• Difficult to participate in the trial by the investigator

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase I Monotherapy Cohort; Participants receive GAIA-102 as monotherapy.	Biological: GAIA-102; GAIA-102: 1 vial (2 x 10^8 cells) as dose at a fixed dose, on 1 to 3 times by weekly for 3 consecutive weeks.; Biological: GAIA-102; GAIA-102: 1 vial (2 x 10^8 cells) as dose at a fixed dose, on 3 times by weekly for 3 consecutive weeks.
Experimental: Phase I Combination Cohort; Participants receive GAIA-102 in combination with pembrolizumab.	Biological: GAIA-102; GAIA-102: 1 vial (2 x 10^8 cells) as dose at a fixed dose, on 1 to 3 times by weekly for 3 consecutive weeks.; Biological: GAIA-102; GAIA-102: 1 vial (2 x 10^8 cells) as dose at a fixed dose, on 3 times by weekly for 3 consecutive weeks.; Drug: Pembrolizumab; Pembrolizumab 200 mg administered on Day 1.; Drug: Pembrolizumab; Pembrolizumab 200 mg administered on Day 8.
Experimental: Phase II Gastric Cancer Part: GAIA-102 and Pembrolizumab Combination Group; Participants receive GAIA-102 in combination with pembrolizumab.	Biological: GAIA-102; GAIA-102: 1 vial (2 x 10^8 cells) as dose at a fixed dose, on 1 to 3 times by weekly for 3 consecutive weeks.; Biological: GAIA-102; GAIA-102: 1 vial (2 x 10^8 cells) as dose at a fixed dose, on 3 times by weekly for 3 consecutive weeks.; Drug: Pembrolizumab; Pembrolizumab 200 mg administered on Day 1.; Drug: Pembrolizumab; Pembrolizumab 200 mg administered on Day 8.
Active Comparator: Phase II Gastric Cancer Part: Ttrifluridine/tipiracil hydrochloride (FTD/TPI)Control Group; Participants receive trifluridine/tipiracil hydrochloride (FTD/TPI).	Drug: Trifluridine/tipiracil hydrochloride (FTD/TPI); Trifluridine/tipiracil hydrochloride (FTD/TPI) will be administered orally twice daily for 5 consecutive days, followed by a 2-day rest period. This cycle will be repeated twice, followed by a 14-day rest period. One course consists of this schedule, and the treatment will be repeated in cycles.
Experimental: Phase II Pancreatic Cancer Part:GAIA-102 and Pembrolizumab Added to Standard Therapy Group; Participants receive GAIA-102 in combination with pembrolizumab, irinotecan hydrochloride hydrate, calcium levofolinate hydrate, and fluorouracil.	Biological: GAIA-102; GAIA-102: 1 vial (2 x 10^8 cells) as dose at a fixed dose, on 1 to 3 times by weekly for 3 consecutive weeks.; Biological: GAIA-102; GAIA-102: 1 vial (2 x 10^8 cells) as dose at a fixed dose, on 3 times by weekly for 3 consecutive weeks.; Drug: Pembrolizumab; Pembrolizumab 200 mg administered on Day 1.; Drug: Pembrolizumab; Pembrolizumab 200 mg administered on Day 8.; Drug: Irinotecan hydrochloride hydrate; Intravenous infusion of 70 mg/m² (based on body surface area) over 90 minutes at 2-week intervals.; Drug: Calcium levofolinate hydrate; Intravenous infusion of 200 mg/m² (based on body surface area) over 2 hours.; Drug: Fluorouracil; Immediately after completion of the calcium levofolinate hydrate intravenous infusion, fluorouracil 400 mg/m² (based on body surface area) will be administered by intravenous injection, followed by a continuous intravenous infusion of fluorouracil 2,400 mg/m² (based on body surface area) over 46 hours.
Active Comparator: Phase II Pancreatic Cancer Part:Standard Therapy Group; Participants receive standard therapy consisting of irinotecan hydrochloride hydrate, calcium levofolinate hydrate, and fluorouracil.	Drug: Irinotecan hydrochloride hydrate; Intravenous infusion of 70 mg/m² (based on body surface area) over 90 minutes at 2-week intervals.; Drug: Calcium levofolinate hydrate; Intravenous infusion of 200 mg/m² (based on body surface area) over 2 hours.; Drug: Fluorouracil; Immediately after completion of the calcium levofolinate hydrate intravenous infusion, fluorouracil 400 mg/m² (based on body surface area) will be administered by intravenous injection, followed by a continuous intravenous infusion of fluorouracil 2,400 mg/m² (based on body surface area) over 46 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants of Dose Limiting Toxicity (DLT) with GAIA-102 (Phase I)	DLT was evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and is defided following events: 1. Grade 4 hemotoxicity or hemotoxicity requiring blood transfusion. 2. Grade 3 or higher non-hematoxicity	Cycle 1 (Cycle period is 28 days)
Frequency and severity of adverse events(Phase I)		2 year
Overall survival in patients with gastric cancer (Phase II)		up to 4 years
Overall survival in patients with pancreatic cancer (PhaseⅡ)		up to 5 years(up to 5.5 years for the Run-in Cohort）

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival(Phase I)		2 year
Pharmacokinetics of GAIA-102(Phase I)	The following metrics were meassured as pharmcokinetics; Cmax: The peak plasma concentration of a drug after administration.; tmax. : Time to reach Cmax; Cmin: The lowest (trough) concentration that a drug reaches before the next dose is administered.	pre-dose
Biomarker of GAIA-102(Phase I)	Protein expression levels are measured in ascites and blood as biomarkers. The following are the markers to be measured; CCL3/CCL4/CCL5/CCL20/CXCL9/CXCL10/CXCL11	pre-dose
Biomarker of GAIA-102(Phase II)	Protein expression levels are measured in ascites and blood as biomarkers. The following are the markers to be measured; CCL3/CCL4/CCL5/CCL20/CXCL9/CXCL10/CXCL11	pre-dose
Overall Survival Period(Phase I)		2 year
Objective Response Rate （ORR) and Disease Control Rate (DCR)(Phase I)	Disease control rate based on RECIST version 1.1. DCR is defined as the proportion of participants whose best overall response (BOR) is Complete Response (CR), Partial Response (PR), or Stable Disease (SD) during the first 24 weeks after the initial administration of study treatment. Stable disease is defined as meeting the RECIST v1.1 criteria for SD at least once at any time point 8 weeks or more after study registration.	Up to 24 weeks after first dose
Objective Response Rate and Disease Control Rate(Phase II)	Disease control rate based on RECIST version 1.1. DCR is defined as the proportion of participants whose best overall response (BOR) is Complete Response (CR), Partial Response (PR), or Stable Disease (SD) during the first 24 weeks after the initial administration of study treatment. Stable disease is defined as meeting the RECIST v1.1 criteria for SD at least once at any time point 8 weeks or more after study registration.	up to 24 weeks after first dose
Progression-free Survival (Phase II)		up to 4 years for patients with gastric cancer and up to 5 years for patients with pancreatic cancer (up to 5.5 years for the Run-in Cohort).
Objective Response Period and Period until Objective Response (Phase II)		up to 2 years
One-year survival rate in patients (Phase II)		1 year
Frequency and severity of adverse events (Phase II)		up to 4 years for patients with gastric cancer and up to 5 years for patients with pancreatic cancer (up to 5.5 years for the Run-in Cohort).

Collaborators and Investigators

• Sponsor: Kyushu University
• Collaborators: Japan Agency for Medical Research and Development; GAIA BioMedicine Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2022
• Primary Completion (Estimated): March 31, 2032
• Study Completion (Estimated): March 31, 2032

Study Registration Dates

• First Submitted: June 13, 2022
• First Submitted That Met QC Criteria: June 24, 2022
• First Posted (Actual): June 30, 2022

Study Record Updates

• Last Update Posted (Actual): September 15, 2026
• Last Update Submitted That Met QC Criteria: September 13, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Endocrine Gland Neoplasms; Pancreatic Diseases; Stomach Neoplasms; Pancreatic Neoplasms; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleic Acids, Nucleotides, and Nucleosides; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Uracil; Pyrimidinones; Deoxyribonucleosides; Thymidine; Fluorouracil; Trifluridine; pembrolizumab
• Other Study ID Numbers: CTR024-001

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No