Dose-escalation Study to Evaluate the Safety and Tolerability of GX-I7 in Patients With Glioblastoma (GBM)

A Phase 1b, Dose-escalation Study to Evaluate the Safety, Tolerability, and the Lymphocyte Increasing Effects of GX-I7 Intramuscular Administration in Patients With Glioblastoma

Patients will be enrolled in two stages:

• Dose-escalation stage: Approximately 12-24 patients will be enrolled.

Study Overview

• Status: Completed
• Conditions: Newly Diagnosed Glioblastoma
• Intervention / Treatment: Drug: GX-I7

Detailed Description

Detailed Description:

• Dose-escalation stage : designed as classical 3+3 to determine MTD(Maximum tolerable dose), RP2D(Recommended Phase 2 Dose) and DLT(Dose-limiting toxicity)s to evaluate approximately four dose levels of GX-I7

• pre-determined dose(Level I)~ pre-determined dose(Level IV)

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seocho
    • Seoul, Seocho, Korea, Republic of, 06591
      • The Catholic University of Korea Seoul St. Mary'S Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

[Inclusion Criteria]

1. Ability to understand and willingness to sign a written informed consent document (ICF).
2. Age ≥ 19 years
3. Able to comply with the study protocol, in the investigator's judgment
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

[Exclusion Criteria] General Exclusion Criteria

1. Unable to comply with study and follow-up procedures
2. Is pregnant or breastfeeding
3. Have clinically significant cardiac disease (New York Heart Association, Class II or greater) including myocardial infarction, unstable arrhythmias, and/or unstable angina in the past 3 months
4. Have clinically significant liver disease, including alcoholic, or other hepatitis, cirrhosis, and inherited liver disease or current alcohol abuse

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

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Patients will receive treatment with GX-I7 at a pre-determined dose (Level I) on Day1 of each cycle.	Drug: GX-I7; During Treatment Period, patients will receive the assigned dose of GX-I7 intramuscular injection every 4~12 weeks per cycle up to 6 cycles in the absence of unacceptable toxicity or clinically compelling evidence of disease progression.
Experimental: Cohort 2; Patients will receive treatment with GX-I7 at a pre-determined dose (Level II) on Day1 of each cycle.	Drug: GX-I7; During Treatment Period, patients will receive the assigned dose of GX-I7 intramuscular injection every 4~12 weeks per cycle up to 6 cycles in the absence of unacceptable toxicity or clinically compelling evidence of disease progression.
Experimental: Cohort 3; Patients will receive treatment with GX-I7 at a pre-determined dose (Level III) on Day1 of each cycle.	Drug: GX-I7; During Treatment Period, patients will receive the assigned dose of GX-I7 intramuscular injection every 4~12 weeks per cycle up to 6 cycles in the absence of unacceptable toxicity or clinically compelling evidence of disease progression.
Experimental: Cohort 4; Patients will receive treatment with GX-I7 at a pre-determined dose (Level IV) on Day1 of each cycle.	Drug: GX-I7; During Treatment Period, patients will receive the assigned dose of GX-I7 intramuscular injection every 4~12 weeks per cycle up to 6 cycles in the absence of unacceptable toxicity or clinically compelling evidence of disease progression.
Experimental: Cohort 5(Dose-expansion); Optimal fixed dose of GX-I7 from Dose-escalation stage on Day1 of each cycle (Maximum tolerable dose or Maximum efficacious dose or Maximum administered dose level or consecutive lower or upper dose level which does not exceed Maximum tolerable dose based on Safety Monitoring Committee(SMC) decision)	Drug: GX-I7; During Treatment Period, patients will receive the assigned dose of GX-I7 intramuscular injection every 4~12 weeks per cycle up to 6 cycles in the absence of unacceptable toxicity or clinically compelling evidence of disease progression.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DLT(Dose-Limiting Toxicity) Assessment	Incidence and nature of DLT(Dose-Limiting Toxicity)s	Through study completion, an average of 2 years
Incidence, nature and severity of Adverse events	Incidence, nature and severity of adverse events graded according to NCI CTCAE v4.0	Through study completion, an average of 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PD(pharmacodynamic) profile [ALC result]	Changes of ALC(Absolute lymphocyte count) from the baseline	Through study completion, an average of 2 years
Anti-tumor Activity [OS]	Objective response(OS) defined as the time from the date of diagnosis to the death from any cause	Through study completion, an average of 2 years
Anti-tumor Activity [PFS]	Progression-free survival (PFS) defined according to iRANO(Immunotherapy Response Assessment for Neuro-Oncology)	Through study completion, an average of 2 years
Immunogenicity[ ADA and neutralizing antibody]	Incidence of anti-GX-I7 antibody (ADA) and neutralizing antibody during the study	Through study completion, an average of 2 years
Exploratory Biomarker [serum Interleukin-7]	Changes in serum Interleukin-7	Through study completion, an average of 2 years

Collaborators and Investigators

• Sponsor: Genexine, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): June 20, 2018
• Primary Completion (Actual): September 25, 2020
• Study Completion (Actual): September 25, 2020

Study Registration Dates

• First Submitted: June 26, 2018
• First Submitted That Met QC Criteria: August 6, 2018
• First Posted (Actual): August 7, 2018

Study Record Updates

• Last Update Posted (Actual): November 10, 2020
• Last Update Submitted That Met QC Criteria: November 8, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Phase 1b
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Glioblastoma
• Other Study ID Numbers: GX-I7-CA-004

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No