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

Study Overview
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Brief Summary
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Patients will be enrolled in two stages: Dose-escalation stage: Approximately 12-24 patients will be enrolled.

Detailed Description
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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)

Official Title
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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

Conditions
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Newly Diagnosed Glioblastoma

Intervention / Treatment
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* Drug: GX-I7


Participation Criteria
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Eligibility Criteria
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[Inclusion Criteria] Ability to understand and willingness to sign a written informed consent document (ICF). Age ≥ 19 years Able to comply with the study protocol, in the investigator's judgment Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. [Exclusion Criteria] General Exclusion Criteria Unable to comply with study and follow-up procedures Is pregnant or breastfeeding 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 Have clinically significant liver disease, including alcoholic, or other hepatitis, cirrhosis, and inherited liver disease or current alcohol abuse

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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>Patients will receive treatment with GX-I7 at a pre-determined dose (Level I) on Day1 of each cycle. | Drug: GX-I7<br>* 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.<br>|
| Experimental: Cohort 2<br>Patients will receive treatment with GX-I7 at a pre-determined dose (Level II) on Day1 of each cycle. | Drug: GX-I7<br>* 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.<br>|
| Experimental: Cohort 3<br>Patients will receive treatment with GX-I7 at a pre-determined dose (Level III) on Day1 of each cycle. | Drug: GX-I7<br>* 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.<br>|
| Experimental: Cohort 4<br>Patients will receive treatment with GX-I7 at a pre-determined dose (Level IV) on Day1 of each cycle. | Drug: GX-I7<br>* 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.<br>|
| Experimental: Cohort 5(Dose-expansion)<br>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<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase 1b