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

Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02499224
• Other study ID #: NOV110501-101
• Status: Completed
• Phase: Phase 1
• Start date: July 13, 2015
• Est. completion date: July 4, 2018

Study information

• Verified date: March 2016
• Source: CellabMED
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: July 4, 2018
• Est. primary completion date: July 4, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors

Intervention

Drug:
• YYB101
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

Locations

Country	Name	City	State
Korea, Republic of	Samsung Medical Center	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
CellabMED

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serum HGF Concentration profile according to YYB101 dosing		By 12 months after enrollment of the last subject
Other	Tissue cMET expression level before YYB101 dosing	Tissue cMET expression level and efficacy (Best overall response, Progress-free survival, Disease control rate)	By 12 months after enrollment of the last subject
Primary	Dose-escalation cohort: DLTs and MTD		28 days
Secondary	Incidence of AEs that result in discontinuation and dose reduction of YYB101		By 12 months after enrollment of the last subject
Secondary	Clinical laboratory abnormalities that result in discontinuation and dose reduction of YYB101		By 12 months after enrollment of the last subject
Secondary	Vital sign that result in discontinuation and dose reduction of YYB101		By 12 months after enrollment of the last subject
Secondary	Anti-YYB101 antibody that result in discontinuation and dose reduction of YYB101		By 12 months after enrollment of the last subject
Secondary	Area under the plasma concentration versus time curve (AUC) of YYB101		By 4 and 8 weeks after last administration, average 16 weeks
Secondary	Peak Plasma Concentration (Cmax) of YYB101		By 4 and 8 weeks after last administration, average 16 weeks