Safety and Pharmacokinetics Study of YYB101 in Advanced Solid Tumors Patients Who Are Refractory to Standard Therapy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and maximum tolerated dose (MTD) of YYB101, HGF-neutralizing humanized Mab, in advanced solid tumors patients who are refractory to standard therapy.

Detailed Description
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To evaluate the safety, tolerability, and pharmacokinetics of YYB101, patients who are refractory to standard therapy will be enrolled in this study. In dose-escalation cohort, subjects will be enrolled sequentially into four dose cohorts receiving a single dose of YYB101 (0.3, 1, 3, or 5 mg/kg; 3 or 6 subjects per dose cohort) and will be entered the 4-week treatment-free period to evaluate safety and pharmacokinetics. If no dose-limiting toxicity (DLT) is observed during the 4-week period, YYB101 administration will be resumed at the same dose level every 2 weeks until disease progression or unacceptable toxicity development. After the completion of the dose-escalation cohort, additional subjects will be enrolled into a dose-expansion cohort at the maximum tolerated dose (MTD) or recommended phase II dose (RP2D) for further exploration of safety, tolerability, efficacy and pharmacodynamics.

Official Title
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A Phase I Study to Assess the Safety, Tolerability, and Pharmacokinetics of YYB101, Hepatocyte Growth Factor (HGF)-Neutralizing Humanized Monoclonal Antibody (Mab), in Advanced Solid Tumors Patients Who Are Refractory to Standard Therapy

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: YYB101


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients aged 19 years or older Patients with pathologically or cytologically confirmed advanced solid tumor which is refractory to standard treatment or for which there is no standard therapy ECOG performance status ≤ 2 Life expectancy of ≥ 12 weeks Adequate hematologic, hepatic and renal functions as follows: ANC ≥ 1,500/µL (without G-CSF support within 2 weeks before IP administration) Platelet ≥ 100,000/µL (without transfusion within 2 weeks before IP administration) Hemoglobin ≥ 10.0 g/dL (without transfusion within 4 weeks before IP administration) Serum creatinine ≤ 1.5 mg/dL or eGRF ≥ 60 mL/min/1.73 m2 AST and ALT ≤ 2.5 x ULN (AST and ALT ≤ 5 x ULN in the presence of liver metastasis or hepatocarcinoma) Total bilirubin ≤ 1.5 x ULN (with exception of the case associated with Gilbert's syndrome) PT and aPTT ≤ 1.5 x ULN UPC < 1.0 (g/g) (requiring if protein ≥ 1 positive (+) in urinalysis) Patients who voluntarily give written informed consent Exclusion Criteria: Patients with hematologic malignancies including lymphoma Chemo-, radio-chemo-, biologic-, immuno- or radiotherapy for advanced solid tumor within 4 weeks (or nitrosoureas, mitomycin within 6 weeks or targeted biological antibody within 8 weeks) before IP administration Patients had received high-dose chemotherapy requiring hematopoietic progenitor cell support within 2 years before IP administration Patients with symptomatic central nervous system (CNS) metastasis (patients who are radiologically and neurologically stable condition for ≥ 4 weeks and discontinued corticosteroids at least 4 week before IP administration are able to participate in this trial.) History of deep vein thrombosis or pulmonary embolism within 1 year; Cytomegalovirus (CMV), Epstein-Barr virus (EBV), acute coronary syndrome (including unstable angina or myocardial infarction), or clinically significant cerebrovascular disease (including stroke) within 6 month; Major surgery requiring general anesthesia or respiratory assist within 4 weeks (or video-assisted thoracoscopic surgery or open-and-closed surgery within 2 weeks) before IP administration Concurrent NYHA class III or IV heart failure, uncontrolled hypertension, poorly controlled arrhythmia, other clinically significant cardiovascular abnormalities at investigator's discretion (e.g. LVEF < 50%, clinical significant abnormalities of heart wall, or cardiac muscle damage), known positive result for HIV or other uncontrolled active infection disease Requirement for continuous non-steroidal anti-inflammatory drugs (NSAIDs) or systemic corticosteroids Receiving anticoagulant, history of bleeding diathesis, massive hemoptysis, gastrointestinal hemorrhage, or peptic ulcer disease (< 325 mg aspirin is acceptable) History of severe drug hypersensitivity or hypersensitivity to IP or similar Mab Pregnancy or breast-feeding Women of childbearing potential (WOCBP) or men who are unwilling to use adequate contraception or be abstinent during the trial and for at least 2 months after the end of treatment Patients who received investigational product or investigational device in other clinical trials within 3weeks prior to participation in this trial Patients who cannot participate in this trial at the investigator's discretion

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: YYB101<br>Dose-escalation cohort: YYB101 of each dose level (0.3mg/kg to 5mg/kg), IV infusion on Day 1, Day 29, and followed by every 2 weeks Dose-expansion cohort: YYB101 of MTD (or RP2D), IV infusion every 2 weeks | Drug: YYB101<br>* Dose-escalation cohort: YYB101 of each dose level (0.3mg/kg to 5mg/kg), IV infusion on Day 1, Day 29, and followed by every 2 weeks until disease progression or unacceptable toxicity development. Dose-expansion cohort: YYB101 of MTD (or RP2D), IV infusion every 2 weeks until disease progression or unacceptable toxicity development<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-escalation cohort: DLTs and MTD |  | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of AEs that result in discontinuation and dose reduction of YYB101 |  | By 12 months after enrollment of the last subject | 
| Clinical laboratory abnormalities that result in discontinuation and dose reduction of YYB101 |  | By 12 months after enrollment of the last subject | 
| Vital sign that result in discontinuation and dose reduction of YYB101 |  | By 12 months after enrollment of the last subject | 
| Anti-YYB101 antibody that result in discontinuation and dose reduction of YYB101 |  | By 12 months after enrollment of the last subject | 
| Area under the plasma concentration versus time curve (AUC) of YYB101 |  | By 4 and 8 weeks after last administration, average 16 weeks | 
| Peak Plasma Concentration (Cmax) of YYB101 |  | By 4 and 8 weeks after last administration, average 16 weeks |