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

• ClinicalTrials.gov Identifier: NCT02499224
• Recruitment Status: Completed
• First Posted: July 16, 2015
• Last Update Posted: May 13, 2021
• Sponsor: CellabMED
• Information provided by (Responsible Party): CellabMED

Tracking Information

• First Submitted Date: May 14, 2015
• First Posted Date: July 16, 2015
• Last Update Posted Date: May 13, 2021
• Actual Study Start Date: July 13, 2015
• Actual Primary Completion Date: July 4, 2018 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: July 13, 2015): Dose-escalation cohort: DLTs and MTD [ Time Frame: 28 days ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 13, 2015)

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

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: July 13, 2015)

• Serum HGF Concentration profile according to YYB101 dosing [ Time Frame: By 12 months after enrollment of the last subject ]
• Tissue cMET expression level before YYB101 dosing [ Time Frame: By 12 months after enrollment of the last subject ]
  Tissue cMET expression level and efficacy (Best overall response, Progress-free survival, Disease control rate)

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

• Brief Title: Safety and Pharmacokinetics Study of YYB101 in Advanced Solid Tumors Patients Who Are Refractory to Standard Therapy
• 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
• 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.
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: 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

Study Arms

Experimental: 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 Dose-expansion cohort: YYB101 of MTD (or RP2D), IV infusion every 2 weeks

Intervention: Drug: YYB101

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: July 13, 2015): 39
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: July 4, 2018
• Actual Primary Completion Date: July 4, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 19 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Korea, Republic of

Administrative Information

• NCT Number: NCT02499224
• Other Study ID Numbers: NOV110501-101
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: CellabMED
• Original Responsible Party: National OncoVenture
• Current Study Sponsor: CellabMED
• Original Study Sponsor: National OncoVenture
• Collaborators: Not Provided

Investigators

• Study Director: Kim Jung Yong, MD, Ph.D; National OncoVenture/National Cancer Center
• Study Director: Hong SungHee, MS; National OncoVenture/National Cancer Center

• PRS Account: CellabMED
• Verification Date: March 2016