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

NCT02499224 | Completed Phase 1 DMC

• 1 other identifier: NOV110501-101
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

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.

Conditions

Solid Tumors

Outcome Measures

Primary Outcomes (1)

• Dose-escalation cohort: DLTs and MTD

  28 days

Secondary Outcomes (6)

• 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

Other Outcomes (2)

• 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

Study Arms (1)

YYB101

EXPERIMENTAL

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

Interventions

YYB101 DRUG

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

YYB101

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• CellabMED: lead

Study Sites (1)

Samsung Medical Center

Seoul, 135-710, South Korea

Location

Related Publications (1)

• Kim ST, Hong JY, Park SH, Park JO, Park YW, Park N, Lee H, Hong SH, Lee SJ, Song SW, Kim K, Park YS, Lim HY, Kang WK, Nam DH, Lee JW, Park K, Kim KM, Lee J. First-in-human phase I trial of anti-hepatocyte growth factor antibody (YYB101) in refractory solid tumor patients. Ther Adv Med Oncol. 2020 Jun 2;12:1758835920926796. doi: 10.1177/1758835920926796. eCollection 2020.

  PMID: 32536979 DERIVED

MeSH Terms

Interventions

monoclonal antibody YYB-101

Study Officials

• Kim Jung Yong, MD, Ph.D

  National OncoVenture/National Cancer Center

  STUDY DIRECTOR

• Hong SungHee, MS

  National OncoVenture/National Cancer Center

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2015
• First Posted: July 16, 2015
• Study Start: July 13, 2015
• Primary Completion: July 4, 2018
• Study Completion: July 4, 2018
• Last Updated: May 13, 2021

Record last verified: 2016-03

Data Sharing

• IPD Sharing: Will not share

Locations

KR (1)