Study to Evaluate Safety and Tolerability of GX-I7 in Patients With Locally Advanced or Metastatic Solid Tumors

Study Overview
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Brief Summary
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Patients will be enrolled in two stages: Dose-escalation stage: Approximately 15-30 patients will be enrolled. Dose-expansion stage: 6-12 patients will be enrolled. Dose-escalation slots will be filled first, then dose-expansion slots.

Detailed Description
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Dose-escalation stage : designed as classical 3+3 to determine MTD or RP2D to evaluate approximately GX-I7. Dose-expansion stage : designed to enroll additional 6-12 patients to acquire additional safety and pharmacodynamic data to more fully inform the dose selection for RP2D

Official Title
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A Phase 1b, Open Label, Dose-escalation Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GX-I7 in Patients With Locally Advanced or Metastatic Solid Tumors

Conditions
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Locally Advanced or Metastatic Solid Tumors

Intervention / Treatment
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* Drug: GX-I7


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed Informed Consent Form (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 Life expectancy ≥ 12 weeks Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment (Cycle 1, Day 1) Serum pregnancy test for women of childbearing potential (including women who have had a tubal ligation) must be performed and documented as negative within 14 days prior to Cycle 1, Day 1 For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm Patients with histologic documentation of locally advanced, recurrent, or metastatic incurable solid tumors that has progressed after at least one available standard therapy; or for whom standard therapy has proven to be ineffective or intolerable, or is considered inappropriate Patients with measurable disease per RECIST v1.1 Exclusion Criteria: Inability to comply with study and follow-up procedures Pregnancy, lactation, or breastfeeding Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, and/or unstable angina Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis, cirrhosis, and inherited liver disease or current alcohol abuse Poorly controlled Type 2 diabetes mellitus defined as a screening hemoglobin A1C ≥ 8% or a fasting plasma glucose ≥ 160 mg/dL (or 8.8 mmol/L) Major surgical procedure within 28 days prior to Cycle 1, Day 1, or anticipation of need for a major surgical procedure during the study Any anti-cancer therapy, whether investigational or approved, including chemotherapy, hormonal therapy, and/or radiotherapy, within 3 weeks prior to initiation of study treatment Adverse events from prior anti-cancer therapy that have not resolved to Grade ≤ 1 except for alopecia, vitiligo, or endocrinopathy managed with replacement therapy History of autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barre syndrome, multiple sclerosis, vasculitis, or glomerulonephritis Primary CNS malignancy, untreated CNS metastases, or active CNS metastases (progressing or requiring corticosteroids for symptomatic control) History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins

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: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GX-I7<br>Determined dose of GX-I7 on Day1 of each cycle | Drug: GX-I7<br>* GX-I7 25mg/ml/vial<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DLT | Incidence of nature of DLTs | up to 24 months | 
| AE | Incidence, nature and severity of adverse events graded according to NCI CTCAEv4.0 | up to 24 months | 
| ECG test evaluated by QTc | Change QTc from baseline (> 500 msec) | up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) profile | Serum concentration of GX-I7 at specified timepoints for the Area under the concentration time-curve (AUC) | up to cycle 3 day 1(approximately 9 weeks) | 
| Anti-tumor activity | Objective response, defined as a complete response (CR) or partial response (PR) per RECIST v.1.1, as determined by the investigator | up to 24 months | 
| Immunogenicity | Incidence of anti-drug antibodies (ADAs) during the study | up to 24 months | 
| Exploratory Biomarker | Changes in immune infiltrates, immune-related gene expression in tumor tissue prior to and during study treatment | up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Phase1b