GIC-102, Intravenous Allogeneic NK Cells, in Subjects With Advanced Solid Cancers and R/R Hematologic Malignancies

An Open-label, Multi-center, Dose-escalation and Expansion, Phase 1/2a Study to Evaluate the Safety, Tolerability, PK/PD, and Preliminary Anti-tumor Activity of GIC-102 Monotherapy in Patients With Advanced Solid Tumors, R/R Non-Hodgkin Lymphoma, and Multiple Myeloma

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors; Relapsed/Refractory Multiple Myeloma; Relapsed/Refractory Non-Hodgkin Lymphoma
• Intervention / Treatment: Drug: GIC-102

Detailed Description

This is a first-in-human, open-label, non-randomized, dose-escalation and expansion phase 1/2a 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.

This study will comprise two phases.

• GIC-102 monotherapy dose escalation Phase
• GIC-102 monotherapy dose expansion phase

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.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of
    • Recruiting
    • Seoul National University Hospital
    • Contact: Youngil Koh, M.D Ph.D; Phone Number: +82 02-6072-5206; Email: go01@snu.ac.kr
  • Seoul, Korea, Republic of
    • Recruiting
    • Korea University Anam Hospital
    • Contact: Soo-Hyeon Lee, M.D Ph.D; Phone Number: +82 02-920-5690; Email: soohyeon_lee@korea.ac.kr
  • Seoul, Korea, Republic of
    • Not yet recruiting
    • Seoul ASAN Medical Center
    • Contact: Jae-Lyun Lee, M.D Ph.D; Phone Number: +82-3010-5977; Email: jaelyun@amc.seoul.kr
  • Seoul, Korea, Republic of
    • Recruiting
    • Seoul ASAN Medical Center
    • Contact: Dok-Hyun Yoon, M.D Ph.D; Phone Number: +82 02-3010-5940; Email: dhyoon@amc.seoul.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria:

1. At least 19 years of age
2. Advanced solid tumors, relapsed/refractory non-hodgkin lymphoma, and multiple myeloma
3. At least one measurable or evaluable lesion
4. Eastern Cooperative Oncology Group performance status 0 or 1
5. A life expectancy of 12 weeks or more
6. Acceptable hematological function, kidney, and liver function
7. Subjects who sign on an informed consent form willingly

Exclusion Criteria:

1. Clinically significant cardiovascular disease within 24 weeks
2. Primary malignant tumor other than the indications for this study

3. The following diseases

   1. Severe infection or other uncontrolled active infectious disease requiring administration of systemic antibiotics or antivirals within 4 weeks
   2. The New York Heart Association class III/IV
   3. Active hepatitis B virus or hepatitis C virus infection
   4. Human immunodeficiency virus positive
   5. Clinically significant symptoms or uncontrolled central nervous system metastasis
4. 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
5. Received chemotherapy other than pre-conditioning within 4 weeks
6. Underwent major surgery within 4 weeks prior or minor surgery within 2 weeks
7. Hypersensitivity reactions to the study drug or excipients
8. Hypersensitivity to cyclophosphamide or fludarabine
9. Have received allogeneic cell therapy within 6 months or autologous stem cell therapy within 4 weeks
10. Have previously received an allogeneic tissue/solid organ transplant
11. Have administered other investigational drug or applied other investigational medical device within 4 weeks
12. Pregnant or lactating female subjects
13. Male subjects who did not agree to use contraception or to maintain abstinence

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation phase: GIC-102 monotherapy; Low Dose level 1: 1 x 10^9 cells; Mid Dose level 2: 3 x 10^9 cells; High Dose level 3: 1 x 10^10 cells	Drug: GIC-102; GIC-102 will be administered via IV infusion 3 times at intervals of 1 week, and 28 days is defined as 1 cycle
Experimental: Dose expansion phase: GIC-102 monotherapy; - Dose level: RP2D	Drug: GIC-102; GIC-102 will be administered via IV infusion 3 times at intervals of 1 week, and 28 days is defined as 1 cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity assessment (dose escalation phase)	To determine the maximum tolerated dose of allogeneic natural killer cells	Up to 4 weeks
Adverse event / Immune related adverse event	To determine the safety of GIC-102	through study completion, an average of 1 year
Objective Response Rate (ORR) (dose expansion phase)	To evaluate the efficacy of GIC-102 according to RECISTv1.1(solid tumor), Lugano 2014 (non-Hodgkin's lymphoma), IMWG 2016 (multiple myeloma)	through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate (ORR) (dose escalation phase)	To evaluate the efficacy of GIC-102 according to RECISTv1.1(solid tumor), Lugano 2014 (non-Hodgkin's lymphoma), IMWG 2016 (multiple myeloma)	through study completion, an average of 1 year
Progression free survival (PFS)	Duration from start of study treatment to progression diease or death (regardless of cause), whichever comes first	Through study completion / 6-month, 12-month, 18-month (solid tumor, dose expansion phase)
Overall survival (OS)	Duration from start of study treatment to death (regardless of cause)	Through study completion / 6-month, 12-month, 18-month, overall timepoint(dose expansion phase)
Duration of response (DOR)	Time from the first occurrence of a documented objective response to the time of the first document disease progression or death from any cause	Through study completion
Disease Control Rate (DCR)	Percentage of patients who have achieved CR, PR and stable disease (SD)	through study completion, an average of 1 year
PK Profile (dose expansion phase) -Cmax		up to 6 months
PK Profile (dose expansion phase) - Tmax		up to 6 months
PK Profile (dose expansion phase) - AUC		up to 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PK Profile (dose escalation phase) -Cmax		up to 6 months
PK Profile (dose escalation phase) - Tmax		up to 6 months
PK Profile (dose escalation phase) - AUC		up to 6 months
Immune Profile	Immune response activation factor (Immune subset marker, cytokine expression); Immunophenotyping of peripheral blood mononuclear cells will be performed by flow cytometry	through study completion, an average of 1 year
Alloantibody Identification	donor human leukocyte antigen (HLA) class I-specific antibody (positive/negative); donor HLA class II-specific antibody (positive/negative)	through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: GI Cell, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 28, 2023
• Primary Completion (Estimated): December 30, 2025
• Study Completion (Estimated): June 30, 2026

Study Registration Dates

• First Submitted: April 24, 2023
• First Submitted That Met QC Criteria: May 18, 2023
• First Posted (Actual): May 30, 2023

Study Record Updates

• Last Update Posted (Actual): July 9, 2024
• Last Update Submitted That Met QC Criteria: July 4, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Lymphoma; Multiple Myeloma; Neoplasms, Plasma Cell; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: GIC-102101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No