The purpose of this study is to determine the maximum tolerated dose(MTD)/Recommended Phase 2 Dose(RP2D) and to evaluate the safety and tolerability of GC1118 when given by intravenous (IV) infusion to patients with stage IV solid tumors. The study will also evaluate pharmacokinetics, immunogenicity and antitumor effect of GC1118 and explore prognostic biomarkers and pharmacodynamic biomarkers.
An open-label, single-arm, multi-center, phase 1, dose-escalation study will be conducted to define the MTD/RP2D, safety, PK, immunogenicity and antitumor activity of GC1118 in patients with refractory disease for whom no standard therapy is available. This study is in three parts: a dose escalation segment (Part A), a cohort expansion (Part B) and biweekly administration(Part C). In part A, a dose escalation schema will be applied in dose level cohorts. GC1118 will be administered weekly on Study Day 1, 8, 15, and 22 of each 28-day cycle by IV infusion. Dose escalation may occur as described in the study protocol. Once the MTD has been established during Part A, the MTD cohort will be expanded in part B. And GC1118 will be administered biweekly on Study Day 1, 15 each 28-day cycle by IV infusion in part C. Study assessments will include AE monitoring including physical examination, vital signs and clinical laboratory tests, ECG monitoring, PK analysis of serum GC1118, an assessment of potential anti-GC1118 antibody response and an exploration of potential prognostic and pharmacodynamic biomarkers. Tumor response assessments using Study Day 36 CT/MRI scans will be performed approximately five weeks after the first GC1118 dose for each patient (Part A only). Patients with evidence of disease regression (partial or complete response or stable disease by RECIST criteria) will be allowed to continue therapy at the same dose. Subsequent cycles will consist of administration of GC1118 on Day 1, 8, 15, and 22 of each 28-day cycle with tumor evaluation every other cycle (approximately every 8 weeks) in part A,B and Day 1, 15 of each 28-day cycle with tumor evaluation every other cycle (approximately every 8 weeks) in part C.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
For Part A, GC1118 will be administered by IV infusion once per week for 4 weeks (28-day cycles) in the dose escalation cohorts, starting 0.3mg/kg until Maximum Tolerated Dose is defined. For Part B, the defined MTD/RP2D of GC1118 will be administered by IV infusion once per week for 4 weeks (28-day cycles) in patients with stage IV of gastric cancer, colorectal cancer or other cancers. For Part C, GC1118 will be administered by IV infusion once every 2 weeks for 4 weeks (28-day cycles) in patients with all stage IV advanced solid cancers. Part A, Part B and Part C participants who qualify for subsequent cycles will receive continued GC1118 until evidence of progression of disease.
Seoul National University Hospital
Seoul, South Korea
RECRUITINGOccurrence of Dose Limiting Toxicity (DLT)
Time frame: Approx. 6 months
Frequency of Adverse Events
Time frame: Approx. 6 months
Changes in safety parameters, laboratory values, vital signs and physical examinations
Vital sign assessment will include systolic and diastolic blood pressure, heart rate, respiration rate and temperature. Laboratory values will include hematology and clinical chemistry.
Time frame: Approx. 6 months
Overall Response Rate (ORR) as per Response Evaluation Criteria in Solid Tumors(RECIST) v1.1
Time frame: Approx. 6 months
Disease Control Rate (DCR) as per Response Evaluation Criteria in Solid Tumors(RECIST) v1.1
Time frame: Approx. 6 months
Progression-Free Survival (PFS) as per Response Evaluation Criteria in Solid Tumors(RECIST) v1.1 (Part B)
Time frame: Approx. 6 months
Time versus plasma concentration profiles and basic PK parameters of GC1118
Time frame: Approx. 6 months
Presence of Human Anti Drug Antibody
Assess whether participants develop an immune response to GC1118
Time frame: Approx. 6 months
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NONE
Enrollment
72