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

Phase 1

Recruiting

• Conditions: Gastric Cancer; Pancreatic Cancer
• Interventions: Biological: Phase I part; Biological: Phase II part

• Registration Number: NCT05438459
• Lead Sponsor: Kyushu University

Brief Summary

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 :

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2022-06-08
• Study First Submitted: 2022-06-13
• Study First Submitted QC: 2022-06-24
• Study First Posted: 2022-06-30
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-21
• Last Update Posted: 2025-05-25
• Primary Completion: 2026-12-31
• Study Completion: 2027-06-08

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 96

Inclusion Criteria

1. Unresectable or advanced recurrent gastric cancer with evident peritoneal dissemination on imaging, or with ascites, as well as unresectable or advanced recurrent pancreatic cancer.

2. Refractory/intolerant to more than 3 regimens of therapy for gastric cancer (more than 2 regimens acceptable for Phase II) or more than 2 regimens of therapy for pancreatic cancer (more than 1 regimen acceptable for Phase II)

3. Abdominal port placement is possible

4. No medical history of serious side effects or allergic reactions to pembrolizumab (only for patients in the pembrolizumab combination cohort)

5. Diagnosed gastric adenocarcinoma or pancreatic cancer with by histological or cytological examination

6. 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

7. Eastern Cooperative Oncology Group (ECOG) Performance status(PS) 0-2

8. Patient aged 20years or older

9. 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

10. Expected to survive for 3 months or more at the enrollment

11. Written informed consent

Exclusion Criteria

1. Untreated cranial metastases.

2. Diagnosed with meningeal carcinomatosis

3. Received allogeneic hematopoietic stem cell transplantation

4. 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.

5. Existence or suspected active autoimmune disease

6. 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

7. 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.

8. Have active double cancer and need treatment for the double cancer

9. Requires treatment as shown in "Unacceptable Combination / Supportive Therapy" during the clinical trial period

10. Have a medical history of severe hypersensitivity to immune checkpoint inhibitors or immune-related adverse events requiring treatment

11. 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

12. 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

13. Scheduled thoracotomy or abdominal surgery during the clinical trial period

14. It is judged that it is difficult to enroll in this study due to clinically significant mental illness.

15. Pregnant women, lactating women, women who are currently pregnant, or have no intention of contraception for 4 months after consent is obtained.

16. Allergic to antibiotics and foreign animal-derived ingredients (pig and mouse)

17. Difficult to participate in the trial by the investigator

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GAIA-102 as a single agent	Phase I part	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.
GAIA-102 and pembrolizumab in combination	Phase I part	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. Pembrolizumab：200 mg on Day 1.
GAIA-102 as a single agent	Phase II part	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.
GAIA-102 and pembrolizumab in combination	Phase II part	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. Pembrolizumab：200 mg on Day 1.
GAIA-102 and pembrolizumab in combination	Phase I part	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. Pembrolizumab：200 mg on Day 1.
GAIA-102 and pembrolizumab in combination	Phase II part	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. Pembrolizumab：200 mg on Day 1.

Primary Outcome Measures

Name	Time	Method
Number of participants of Dose Limiting Toxicity (DLT) with GAIA-102 (Phase I)	Cycle 1 (Cycle period is 28 days)	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
Frequency and severity of adverse events(Phase I)	2 year
Progression Free Survival (PFS) rate at 6 months (Phase II)	Week 24	PFS rate at 6 months was defined as the rate of surviving participants who survived or were not determined as progressive at 6 months from the day of enrollment.

Secondary Outcome Measures

Name	Time	Method
Progression-free Survival(Phase I)	2 year
Objective Response Rate Disease Control Rate(Phase II)	2 year
Progression-free Survival (Phase II)	2 year
Biomarker of GAIA-102(Phase II)	pre-dose	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
Overall Survival (Phase II)	2 year
Biomarker of GAIA-102(Phase I)	pre-dose	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
Objective Response Period and Period until Objective Response (Phase II)	2 year
Frequency and severity of adverse events (Phase II)	2 year
Objective Response Rate （ORR) and Disease Control Rate (DCR)(Phase I)	Week 24
Pharmacokinetics of GAIA-102(Phase I)	pre-dose	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.
Overall Survival(Phase I)	2 year

Trial Locations

Locations (1)

Kyushu University Hospital; 🇯🇵 Fukuoka-shi, Fukuoka, Japan