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

CellabMED

Status and phase: Completed; Phase 1

Conditions: Solid Tumors

Treatments: Drug: YYB101

Study type: Interventional

Funder types: Industry

Identifiers

NCT02499224

NOV110501-101

Details and patient eligibility

About

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.

Full 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.

Enrollment: 39 patients

Sex: All

Ages: 19+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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39 participants in 1 patient group

YYB101

Experimental group

Description:

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

Treatment:

Drug: YYB101