A Study of GIC-102 (Allogeneic Natural Killer Cells) in Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, and Multiple Myeloma

Study Overview
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Brief Summary
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This is a first-in-human trial to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics, and antitumor effects of GIC-102 in patients with advanced solid tumors, relapsed/refractory non-hodgkin lymphoma, and multiple myeloma.

Detailed Description
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This is a first-in-human, open-label, non-randomized, dose-escalation phase 1 trial to determine the safety profile and identify the maximum tolerated dose of GIC-102 in patients with advanced solid tumors, relapsed/refractory non-hodgkin lymphoma, and multiple myeloma. GIC-102 is an off-the-shelf allogeneic natural killer cells isolated from non-HLA-related healthy donor. Natural killer cells are innate immune cells that show strong cytolytic function against physiologically stressed cells such as tumor cells and virus infected cells. Patients will receive at least 2 cycles of GIC-102 (each cycle is 3 treatments at a frequency of once a week, and 28 days is defined as one cycle). After treatment period, patients will undergo follow up for survival every 8 weeks for up to 6 months.

Official Title
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Open-label, Multi-center, Dose-escalation Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics/Pharmacodynamics of GIC-102 in Patients With Advanced Solid Tumors, R/R Non-Hodgkin Lymphoma, and Multiple Myeloma

Conditions
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Advanced Solid Tumors, Relapsed/Refractory Non-Hodgkin Lymphoma, Relapsed/Refractory Multiple Myeloma

Intervention / Treatment
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* Biological: GIC-102 (Allogeneic NK cells)


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: At least 19 years of age Advanced solid tumors, relapsed/refractory non-hodgkin lymphoma, and multiple myeloma At least one measurable or evaluable lesion Eastern Cooperative Oncology Group performance status 0 or 1 A life expectancy of 3 months or more Acceptable hematological function, kidney, and liver function Exclusion Criteria: Clinically significant cardiovascular disease within 6 months Primary malignant tumor other than the indications for this study The following diseases Severe infection or other uncontrolled active infectious disease requiring administration of systemic antibiotics or antivirals within 4 weeks The New York Heart Association class III/IV Active hepatitis B virus or hepatitis C virus infection Human immunodeficiency virus positive Clinically significant symptoms or uncontrolled central nervous system metastasis Previously been diagnosed with immunodeficiency or need systemic corticosteroids or other systemic immunosuppressants within 2 weeks or require administration of systemic immunosuppressants during the study Received chemotherapy other than pre-conditioning within 4 weeks Underwent major surgery within 4 weeks prior or minor surgery within 2 weeks Hypersensitivity reactions to the study drug or excipients Hypersensitivity to cyclophosphamide or fludarabine Have received allogeneic cell therapy within 6 months or autologous stem cell therapy within 4 weeks Have previously received an allogeneic tissue/solid organ transplant Have administered other investigational drug or applied other investigational medical device within 4 weeks Pregnant or lactating female subjects Male subjects who did not agree to use contraception or to maintain abstinence

Ages Eligible for Study
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Minimum Age: 19 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GIC-102<br>On day -5, -4, and -3, patients receive cyclophosphamide 300 mg/m² and fludarabine 30mg/m² every 2 cycles On day 0, patients receive GIC-102 3 times at intervals of 1 week, and 28 days is defined as 1 cycle | Biological: GIC-102 (Allogeneic NK cells)<br>* Dose level 1: 1 x 10^9 cells Dose level 2: 3 x 10^9 cells Dose level 3: 1 x 10^10 cells<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity assessment | To determine the maximum tolerated dose of allogeneic natural killer cells | Up to 1 month | 
| Adverse event / Immune related adverse event | To determine the safety of GIC-102 | Through study completion, approximately 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate and duration of response | To evaluate the efficacy of GIC-102 according to RECISTv1.1(solid tumor), Lugano 2014 (non-Hodgkin's lymphoma), IMWG 2016 (multiple myeloma) | Up to 6 months from the last patient enrolled | 
| Progression free survival | Duration from start of study treatment to progression diease or death (regardless of cause), whichever comes first | Up to 6 months from the last patient enrolled | 
| Overall survival | Duration from start of study treatment to death (regardless of cause) | Up to 6 months from the last patient enrolled |