A Study to Evaluate the Safety and Therapeutic Activity of GI-102 in Patients With Advanced Solid Tumors

An Open-label, Multicenter, Dose Escalation and Expansion Phase 1/2a Study to Evaluate the Safety, Tolerability and Pharmacokinetics, and Therapeutic Activity of GI-102 in Patients With Advanced or Metastatic Solid Tumors

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and therapeutic activity of GI-102 as a single agent over a range of advanced and/or metastatic solid tumors.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumor; Metastatic Solid Tumor
• Intervention / Treatment: Drug: GI-102; Drug: GI-102

Detailed Description

This is a phase 1/2a, open-label, dose-escalation and expansion study to evaluate the safety, tolerability, and anti-tumor effect of GI-102 as a single agent over a range of advanced and/or metastatic solid tumors. This study is adaptive in nature. While GI-102 is being investigated as a single agent in this trial, GI-102 has the potential of being combined with other agents. Based on the data from ongoing nonclinical studies and the dose escalation phase, additional combination therapies [GI-102 + drug(s) X] may be proposed and added to this study protocol via an amendment.

This study will comprise two phases.

• GI-102 monotherapy dose escalation phase
• GI-102 monotherapy dose expansion phase

GI-102 is a novel bi-specific Fc fusion protein containing the CD80 ectodomain as an N-terminal moiety and an interleukin (IL)-2 variant as a C-terminal moiety configurated via a human immunoglobulin G4 (IgG4) Fc. GI-102 has unique characteristics by having bispecificity to CD80 and IL2Rβγ. The CD80 portion is responsible for targeting tumor/immune cells while blocking CTLA-4 expressed on the Treg cells. The IL-2v of GI-102 is designed to abolish IL-2Rα affinity and therefore minimize the effect on Treg while it has very outstanding effect on NK and CD8 T cell proliferation and activity through IL-2Rbr affinity.

• Study Type: Interventional
• Enrollment (Estimated): 92
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Woosun Lee; Phone Number: +82-2-404-2003; Email: Clinical-102@gi-innovation.com
• Study Contact Backup: Name: Jay Kim; Phone Number: +82-2-404-2003; Email: Clinical-102@gi-innovation.com

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
    • Contact: Seock-Ah Im, M.D., Ph.D.
  • Seoul, Korea, Republic of, 05505
    • Recruiting
    • Asan Medical Center
    • Contact: Jae Lyun Lee, M.D., Ph.D.
    • Principal Investigator: Jae Lyun Lee, M.D., Ph.D.
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Samsung Medical Center
    • Principal Investigator: Jeeyun Lee, M.D., Ph.D.
    • Contact: Jeeyun Lee, M.D., Ph.D.
  • Seoul, Korea, Republic of, 03722
    • Recruiting
    • Yonsei University Health System, Severance Hospital
    • Contact: Jung-Yun Lee, M.D., Ph.D.
    • Principal Investigator: Jung-Yun Lee, M.D., Ph.D.
  • Suwon, Korea, Republic of, 12647
    • Recruiting
    • St. Vincent's Hospital
    • Contact: Byoung Yong Shim, M.D., Ph.D.
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85259
      • Recruiting
      • Mayo Clinic in Arizona
      • Contact: Mahesh Seetharam
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic in Florida
      • Contact: Yujie Zhao
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic in Minnesota
      • Contact: Jian Li Campian, PhD.
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
      • Contact: Wen Wee Ma, M.B.B.S

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

• Males and females aged ≥ 18 years (or ≥ 19 years according to local regulatory guidelines) at the time of screening.
• Has adequate organ and marrow function as defined in protocol.
• Measurable disease as per RECIST v1.1.
• ECOG performance status 0-1.
• Adverse events related to any prior chemotherapy, radiotherapy, immunotherapy, other prior systemic anti-cancer therapy, or surgery must have resolved to Grade ≤1, except alopecia and Grade 2 peripheral neuropathy.
• HIV infected patients must be on anti-retroviral therapy (ART) and have a well-controlled HIV infection/disease as defined in protocol.

Key Exclusion Criteria:

• Has known active CNS metastases and/or carcinomatous meningitis.
• An active second malignancy.
• Has active or a known history of Hepatitis B or known active Hepatitis C virus infection.
• Has active tuberculosis or has a known history of active tuberculosis.
• Active or uncontrolled infections, or severe infection within 4 weeks before study treatment administration.
• History of chronic liver disease or evidence of hepatic cirrhosis, except patients with liver metastasis.
• Has an active autoimmune disease that has required systemic treatment in past 2 years.
• Previous immunotherapies related to mode of action of GI-102.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive medications within 2 weeks prior to Cycle 1 Day 1.
• Administration of prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to treatment.
• Radiotherapy within the last 2 weeks before start of study treatment administration, with exception of limited field palliative radiotherapy.
• Administration of a live, attenuated vaccine within 4 weeks before Cycle 1 Day 1.
• Known hypersensitivity to any of the components of the drug products and/or excipients of GI-102.

Other protocol defined inclusion exclusion criteria may apply

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose escalation phase : GI-102 as a single agent; Dose escalation: GI-102, multiple ascending doses	Drug: GI-102; Dose escalation phase: GI-102 will be administered via IV infusion Q3W up to 2 years (approximately 35 cycles).; Drug: GI-102; Dose expansion phase: GI-102 will be administered via IV infusion Q3W up to 2 years (approximately 35 cycles).
Experimental: Dose expansion phase : GI-102 as a single agent; Dose expansion: GI-102, tentative RP2D	Drug: GI-102; Dose escalation phase: GI-102 will be administered via IV infusion Q3W up to 2 years (approximately 35 cycles).; Drug: GI-102; Dose expansion phase: GI-102 will be administered via IV infusion Q3W up to 2 years (approximately 35 cycles).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and nature of Dose-Limiting Toxicity (DLTs) (dose escalation phase)	A DLT is defined as a clinically significant AE (classified according to the NCI CTCAE version 5) or significant laboratory abnormality that occur during the DLT assessment periods, during dose escalation and dose expansion, and is considered by the Investigator to be related to GI-102.	Study Day 1, assessed up to DLT period (3 weeks after treatment)
Incidence, nature, and severity of adverse events (AEs) and immune-related AEs (irAEs) (dose escalation phase)	An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as AEs. All AE events will be graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	Study Day 1, assessed up to approximately 24 months
Objective Response Rate (ORR) (dose expansion phase)	ORR is defined as the percentage of participants with investigator-assessed objective response of complete response (CR) or partial response (PR). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions).	Study Day 1, assessed up to approximately 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and nature of Dose-Limiting Toxicity (DLTs) (dose expansion phase)	A DLT is defined as a clinically significant AE (classified according to the NCI CTCAE version 5) or significant laboratory abnormality that occur during the DLT assessment periods, during dose escalation and dose expansion, and is considered by the Investigator to be related to GI-102.	Study Day 1, assessed up to DLT period (3 weeks after treatment)
Objective Response Rate (ORR) (dose escalation phase)	ORR is defined as the percentage of participants with investigator-assessed objective response of complete response (CR) or partial response (PR). PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum of diameters. CR was defined as disappearance of all target and non-target lesions and normalization of tumor marker levels (as applicable to non-target lesions).	Study Day 1, assessed up to approximately 24 months
Disease Control Rate (DCR)	DCR is defined as the percentage of patients who have achieved CR, PR and stable disease (SD), per RECIST v1.1 guideline as determined by the investigators.	Study Day 1, assessed up to approximately 24 months
Duration of objective response (DoR)	DCR is defined as the time from the first occurrence of a documented objective response to the time of the first document disease progression or death from any cause, whichever occurs first, per RECIST v1.1 as determined by the investigator.	Study Day 1, assessed up to approximately 24 months
Progression-free survival (PFS)	PFS is defined as the time from the first study treatment (Day 1) to the first occurrence of progression or death from any cause, whichever occurs first, per RECIST v1.1 guideline as determined by the investigator	6-month, 12-month, and 18-month
Overall survival (OS)	OS is defined as the time from the first study treatment to death from any cause	12-month and 18-month
Peak plasma concentration (Cmax) of GI-102	Based on the concentration vs time profile by dose level	Study Day 1, assessed up to approximately 24 months
Half-life of GI-102 (T1/2)	Based on the concentration vs time profile by dose level	Study Day 1, assessed up to approximately 24 months
Area under the plasma concentration versus time curve (AUC) of GI-102	Based on the concentration vs time profile by dose level	Study Day 1, assessed up to approximately 24 months
Clearance of GI-102	Based on the concentration vs time profile by dose level	Study Day 1, assessed up to approximately 24 months
Volume of distribution (Vd) of GI-102 after administration	Based on the concentration vs time profile by dose level	Study Day 1, assessed up to approximately 24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of anti-GI-102 antibody (ADA) and neutralizing antibody (Nab)	Serum will be assessed for the presence of ADA and Nab based on the appropriate assay.	Study Day 1, assessed up to approximately 24 months
Immunophenotyping of peripheral blood CD4+ T cells	CD4+ T cells in peripheral blood will be assessed by flow cytometry at various time points	Study Day 1, assessed up to approximately 24 months
Immunophenotyping of peripheral blood CD8+ T cells	CD8+ T cells in peripheral blood will be assessed by flow cytometry at various time points	Study Day 1, assessed up to approximately 24 months
Immunophenotyping of peripheral blood Treg cells	Treg cells in peripheral blood will be assessed by flow cytometry at various time points	Study Day 1, assessed up to approximately 24 months

Collaborators and Investigators

• Sponsor: GI Innovation, Inc.
• Investigators: Study Director: Nari Yun, PhD, GI Innovation, Inc.

Study record dates

Study Major Dates

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

Study Registration Dates

• First Submitted: March 28, 2023
• First Submitted That Met QC Criteria: April 20, 2023
• First Posted (Actual): April 24, 2023

Study Record Updates

• Last Update Posted (Estimated): January 29, 2024
• Last Update Submitted That Met QC Criteria: January 25, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Immunotherapy; IL-2; Interleukin-2; CTLA-4; CD80-IgG4 Fc-IL2 variant; immunocytokine; CD80; GI-102; bispecific protein
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: GII-102-P101

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