Study of ISU104, Targeting ERBB3 in Patients With Advanced Solid Tumors

NCT03552406 | Unknown Phase 1

• 1 other identifier: ISU104-001
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 5

Brief Summary

A phase I, open-label, dose-finding study to assess the safety, tolerability and pharmacokinetics of ISU104, a human monoclonal antibody targeting erbB3 in patients with advanced solid tumors.

Conditions

Solid Tumor

Keywords

Solid tumor; Breast cancer; Head & Neck cancer

Outcome Measures

Primary Outcomes (1)

• Determine the Maximum Tolerated Dose Dependent on Reports of Dose-limiting Toxicities

  Determination of MTD is dependent upon number of cohorts and patients required

  From date of first dose to 4 weeks after administration.

Secondary Outcomes (7)

• Toxicity Evaluation

  through the study completion, an average of 1 year

• Determine Immunogenicity of ISU104

  through the study completion, an average of 1 year

• Determine the Peak Plasma Concentration (Cmax) of ISU104

  up to 12 weeks

• Determine the Area Under the Curve (AUC) of ISU104

  up to 12 weeks

• Explore Overall Response Rate (ORR) of ISU104 or ISU104+Cetuximab

  up to progression, an average 6 months

Study Arms (7)

Dose-Escalation of ISU104 (Dose-Level 1)

EXPERIMENTAL

1 mg/kg; Administered single-dose first week and observation for 4-weeks and then Administered once weekly in a 28-days Cycle

Biological: ISU104

Dose-Escalation of ISU104 (Dose-Level 2)

EXPERIMENTAL

3 mg/kg; Administered single-dose first week and observation for 4-weeks and then Administered once weekly in a 28-days Cycle

Biological: ISU104

Dose-Escalation of ISU104 (Dose-Level 3)

EXPERIMENTAL

5 mg/kg; Administered single-dose first week and observation for 4-weeks and then Administered once weekly in a 28-days Cycle

Biological: ISU104

Dose-Escalation of ISU104 (Dose-Level 4)

EXPERIMENTAL

10 mg/kg; Administered single-dose first week and observation for 4-weeks and then Administered once weekly in a 28-days Cycle

Biological: ISU104

Dose-Escalation of ISU104 (Dose-Level 5)

EXPERIMENTAL

20 mg/kg; Administered single-dose first week and observation for 4-weeks and then Administered once weekly in a 28-days Cycle

Biological: ISU104

Dose-Expansion of ISU104 (Group 1: Monotherapy)

EXPERIMENTAL

ISU104 20 mg/kg to be administered every three weeks (Q3W) as monotherapy

Biological: ISU104

Dose-Expansion of ISU104 (Group 2: Combination therapy)

EXPERIMENTAL

ISU104 20 mg/kg (or decreased dose) Q3W in combination with cetuximab\* 250 mg/m2 QW (\*Initial dose: 400 mg/m2)

Biological: ISU104; Drug: Cetuximab

Interventions

ISU104 BIOLOGICAL

Intravenous Infusion for 1 hour.

Also known as: A human monoclonal antibody targeting ErbB3

Dose-Escalation of ISU104 (Dose-Level 1); Dose-Escalation of ISU104 (Dose-Level 2); Dose-Escalation of ISU104 (Dose-Level 3); Dose-Escalation of ISU104 (Dose-Level 4); Dose-Escalation of ISU104 (Dose-Level 5); Dose-Expansion of ISU104 (Group 1: Monotherapy); Dose-Expansion of ISU104 (Group 2: Combination therapy)

Cetuximab DRUG

Intravenous Infusion for 1 hour (2 hours at initial dose)

Also known as: Erbitux, Epidermal Growth Factor Receptor (EGFR) inhibitor

Dose-Expansion of ISU104 (Group 2: Combination therapy)

Eligibility Criteria

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

You may qualify if:

• Common
• Male or Female with ≥ 19 years of age
• Histologically or Cytologically confirmed a diagnosis of an advanced solid tumor that was refractory to standard treatment or for which no standard therapy existed, or patients declined any treatment options
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Life Expectancy ≥ 12 weeks
• Adequate Hematological, Renal and Hepatic function
• According to Response Evaluation Criteria in Solid Tumors Criteria (RECIST) version 1.1, the patient had at least one measurable lesion

You may not qualify if:

• Severe hypersensitivity or a history of any hypersensitivity to the similar drug class of IP
• Patients underwent the major surgery or procedure, or had the medical history (as blow):
• Major surgery requiring systemic anesthesia or respiratory assist device within 4 weeks prior to baseline \[2 weeks in case of video-assisted thoracoscopic surgery (VATS) or open-and-closed (ONC) surgery)\]
• Severe cardiovascular disease within 24 weeks prior to baseline
• Severe cerebrovascular disease within 24 weeks prior to baseline
• Pulmonary thromboembolism, deep vein thrombosis (DVT) or other clinically and significantly severe lung disease within 24 weeks prior to baseline
• Patients had the following concurrent diseases at baseline:
• Hematologic malignancies including lymphoma
• Clinically significant symptom or uncontrolled central nervous system (CNS) or brain metastases
• Pleural effusion and ascites drainage
• Uncontrolled hypertension (SBP/DBP \> 160/100 mmHg)
• Active hepatitis B or C virus
• Human immunodeficiency virus (HIV) that is positive
• Thromboembolic disease or bleeding diatheses
• Interstitial lung disease (ILD)

Sponsors & Collaborators

• ISU Abxis Co., Ltd.: lead

Study Sites (5)

Kosin University Gospel Hospital

Busan, South Korea

Location

Kyungpook National University Chilgok Hospital

Daegu, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Related Publications (1)

• Seo S, Keam B, Shin SH, Chae YS, Kim TM, Park LC, Hong SB, Ahn MJ, Kim SB. A phase Ia/Ib study of novel anti-ErbB3 monoclonal antibody, barecetamab (ISU104) in refractory solid cancers and monotherapy or in combination with cetuximab in recurrent or metastatic head and neck cancer. Int J Cancer. 2023 Oct 15;153(8):1501-1511. doi: 10.1002/ijc.34622. Epub 2023 Jun 26.

  PMID: 37357950 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Head and Neck Neoplasms

Interventions

Cetuximab; ErbB Receptors

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Receptor Protein-Tyrosine Kinases; Protein-Tyrosine Kinases; Protein Kinases; Phosphotransferases (Alcohol Group Acceptor); Phosphotransferases; Transferases; Enzymes; Enzymes and Coenzymes; Intracellular Signaling Peptides and Proteins; Receptors, Cell Surface; Membrane Proteins; Receptors, Growth Factor; Receptors, Peptide

Study Officials

• Jaehyeon Juhn, Ph.D

  ISU Abxis Co., Ltd.

  STUDY DIRECTOR

Study Design

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

Model Details: A. Part 1: Dose escalation * Total 15 subjects: 3 subjects in each dose level * 1mg/kg/day, 3mg/kg/day, 5mg/kg/day, 10mg/kg/day, 20mg/kg/day B. Part 2: Dose expansion * Group 1 (Mono-therapy: 20 mg/kg/day, Q3W): 6 subjects * Group 2 (Combination therapy with cetuximab 400 mg/m2 followed by 250 mg/m2, Q1W): 12 subjects

Study Record Dates

• First Submitted: May 2, 2018
• First Posted: June 11, 2018
• Study Start: April 27, 2018
• Primary Completion: October 19, 2020
• Study Completion: December 31, 2021
• Last Updated: May 6, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

KR (5)