Solid Tumors
Conditions
Brief summary
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
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.
Interventions
DRUGYYB101
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
Sponsors
CellabMED
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients aged 19 years or older 2. Patients with pathologically or cytologically confirmed advanced solid tumor which is refractory to standard treatment or for which there is no standard therapy 3. ECOG performance status ≤ 2 4. Life expectancy of ≥ 12 weeks 5. 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) 6. Patients who voluntarily give written informed consent
Exclusion criteria
1. Patients with hematologic malignancies including lymphoma 2. 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 3. Patients had received high-dose chemotherapy requiring hematopoietic progenitor cell support within 2 years before IP administration 4. 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.) 5. 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 6. 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 7. Requirement for continuous non-steroidal anti-inflammatory drugs (NSAIDs) or systemic corticosteroids 8. Receiving anticoagulant, history of bleeding diathesis, massive hemoptysis, gastrointestinal hemorrhage, or peptic ulcer disease (\< 325 mg aspirin is acceptable) 9. History of severe drug hypersensitivity or hypersensitivity to IP or similar Mab 10. Pregnancy or breast-feeding 11. 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 12. Patients who received investigational product or investigational device in other clinical trials within 3weeks prior to participation in this trial 13. Patients who cannot participate in this trial at the investigator's discretion
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-escalation cohort: DLTs and MTD | 28 days |
Secondary
| Measure | 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 |
| 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 |
| Anti-YYB101 antibody that result in discontinuation and dose reduction of YYB101 | By 12 months after enrollment of the last subject |
Other
| Measure | Time frame | Description |
|---|---|---|
| Serum HGF Concentration profile according to YYB101 dosing | By 12 months after enrollment of the last subject | — |
| Tissue cMET expression level before YYB101 dosing | By 12 months after enrollment of the last subject | Tissue cMET expression level and efficacy (Best overall response, Progress-free survival, Disease control rate) |
Countries
South Korea
Outcome results
None listed