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

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

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.

Study Overview

• Status: Completed
• Conditions: Locally Advanced or Metastatic Solid Tumors
• Intervention / Treatment: Drug: GX-I7

Detailed Description

• 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

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• Korea, Republic of
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of
    • Seoul St. Mary's Hospital, of the Catholic University

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:

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GX-I7; Determined dose of GX-I7 on Day1 of each cycle	Drug: GX-I7; GX-I7 25mg/ml/vial

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Genexine, Inc.
• Investigators: Principal Investigator: Joo Hyuk Sohn, MD, Yonsei University Health System, Severance Hospital; Principal Investigator: Tae Won Kim, MD, Medical Oncology, Asan Medical Center; Principal Investigator: Myoung-Ah Lee, MD, Medical Oncology, Seoul St. Mary's Hospital, of the Catholic University

Study record dates

Study Major Dates

• Study Start (Actual): March 5, 2018
• Primary Completion (Actual): March 16, 2020
• Study Completion (Actual): March 16, 2020

Study Registration Dates

• First Submitted: January 31, 2018
• First Submitted That Met QC Criteria: March 20, 2018
• First Posted (Actual): March 27, 2018

Study Record Updates

• Last Update Posted (Actual): May 11, 2020
• Last Update Submitted That Met QC Criteria: May 7, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Phase1b
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: GX-I7-CA-003

Drug and device information, study documents

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