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

Study Overview
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Brief Summary
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Phase I Part : Confirm the safety of GAIA-102 GAIA-102 as a single agent 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 single agent 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.

Official Title
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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)

Conditions
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Gastric Cancer, Pancreatic Cancer

Intervention / Treatment
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* Biological: Phase I part
* Biological: Phase II part


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unresectable, advanced and relapsed gastric cancer with malignant ascites or unresectable, advanced and relapsed pancreatic cancer with malignant ascites 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) Abdominal port placement is possible No medical history of serious side effects or allergic reactions to pembrolizumab (only for patients in the pembrolizumab combination cohort) Diagnosed gastric adenocarcinoma or pancreatic cancerwith by histological or cytological examination Negative (MSS= not MSI-high) by microsatellite instability test Eastern Cooperative Oncology Group (ECOG) Performance status(PS) 0-2 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) Serum creatinine <=1.5mg/dL CCr >=30mL/min 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

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GAIA-102 as a single agent<br>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: Phase I part<br>* Administration of GAIA-102 as a single agent or GAIA-102 and pembrolizumab in combination.<br>Biological: Phase II part<br>* Randomized into group of administration of GAIA-102 as a single agent or GAIA-102 or pembrolizumab in combination, group of standard treatment<br>|
| Experimental: GAIA-102 and pembrolizumab in combination<br>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. | Biological: Phase I part<br>* Administration of GAIA-102 as a single agent or GAIA-102 and pembrolizumab in combination.<br>Biological: Phase II part<br>* Randomized into group of administration of GAIA-102 as a single agent or GAIA-102 or pembrolizumab in combination, group of standard treatment<br>|

What is the study measuring?
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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) | 
| Progression Free Survival (PFS) rate at 6 months (Phase II) | 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. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate （ORR) and Disease Control Rate (DCR)(Phase I) |  | Week 24 | 
| Progression-free Survival(Phase I) |  | 2 year | 
| Overall 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 | 
| Objective Response Rate Disease Control Rate(Phase II) |  | 2 year | 
| Progression-free Survival (Phase II) |  | 2 year | 
| Objective Response Period and Period until Objective Response (Phase II) |  | 2 year | 
| Overall Survival (Phase II) |  | 2 year | 
| Frequency and severity of adverse events (Phase II) |  | 2 year | 
| 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 |