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
Overview
- Phase
- Phase 1
- Intervention
- ISU104
- Conditions
- Solid Tumor
- Sponsor
- ISU Abxis Co., Ltd.
- Enrollment
- 33
- Locations
- 5
- Primary Endpoint
- Determine the Maximum Tolerated Dose Dependent on Reports of Dose-limiting Toxicities
- Last Updated
- 4 years ago
Overview
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.
Detailed Description
\[Part 1 Dose-escalation\] This study ams to evaluate the safety, tolerability, and pharmacokinetics of ISU104 in patients with advanced solid tumors. Primary objective To determine recommended Phase II dose (RP2D) of ISU104 based on the results of its safety and tolerability in patients with advanced solid tumors. Secondary objectives 1. To evaluate pharmacokinetics (PK) of ISU104 in patients with advanced solid tumors. 2. To evaluate efficacy of ISU104 in patients with advanced solid tumors. Exploratory purpose To identify the expression of explorable multiple tumor biomarkers and to analyze the relationship between biomarkers and antitumor activity of ISU104. \[Part 2 dose-expansion\] The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of ISU104 in patients with recurrent/metastatic HNSCC (except for nasopharyngeal cancer), when administered intravenously ISU104 alone or ISU104 in combination with cetuximab. Primary objective To determine RP2D of ISU104 based on results of its safety and tolerability in patients with recurrent/metastatic HNSCC (except for nasopharyngeal cancer), when administered intravenously ISU104 only or ISU104 in combination with cetuximab. Secondary objectives 1. To evaluate the pharmacokinetics of ISU104 in patients with recurrent/metastatic HNSCC (except for nasopharyngeal cancer), when administered intravenously ISU104 only or ISU104 in combination with cetuximab. 2. To evaluate the efficacy of ISU104 in patients with recurrent/metastatic HNSCC (except for nasopharyngeal cancer), when administered intravenously ISU104 only or ISU104 in combination with cetuximab. Exploratory purpose To explore a variety of detectable tumor biomarkers and evaluate the relationship between these biomarkers and antitumor activity of ISU104.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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
Exclusion Criteria
- •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
Arms & Interventions
Dose-Escalation of ISU104 (Dose-Level 1)
1 mg/kg; Administered single-dose first week and observation for 4-weeks and then Administered once weekly in a 28-days Cycle
Intervention: ISU104
Dose-Escalation of ISU104 (Dose-Level 2)
3 mg/kg; Administered single-dose first week and observation for 4-weeks and then Administered once weekly in a 28-days Cycle
Intervention: ISU104
Dose-Escalation of ISU104 (Dose-Level 3)
5 mg/kg; Administered single-dose first week and observation for 4-weeks and then Administered once weekly in a 28-days Cycle
Intervention: ISU104
Dose-Escalation of ISU104 (Dose-Level 4)
10 mg/kg; Administered single-dose first week and observation for 4-weeks and then Administered once weekly in a 28-days Cycle
Intervention: ISU104
Dose-Escalation of ISU104 (Dose-Level 5)
20 mg/kg; Administered single-dose first week and observation for 4-weeks and then Administered once weekly in a 28-days Cycle
Intervention: ISU104
Dose-Expansion of ISU104 (Group 1: Monotherapy)
ISU104 20 mg/kg to be administered every three weeks (Q3W) as monotherapy
Intervention: ISU104
Dose-Expansion of ISU104 (Group 2: Combination therapy)
ISU104 20 mg/kg (or decreased dose) Q3W in combination with cetuximab\* 250 mg/m2 QW (\*Initial dose: 400 mg/m2)
Intervention: ISU104
Dose-Expansion of ISU104 (Group 2: Combination therapy)
ISU104 20 mg/kg (or decreased dose) Q3W in combination with cetuximab\* 250 mg/m2 QW (\*Initial dose: 400 mg/m2)
Intervention: Cetuximab
Outcomes
Primary Outcomes
Determine the Maximum Tolerated Dose Dependent on Reports of Dose-limiting Toxicities
Time Frame: From date of first dose to 4 weeks after administration.
Determination of MTD is dependent upon number of cohorts and patients required
Secondary Outcomes
- Explore Overall Response Rate (ORR) of ISU104 or ISU104+Cetuximab(up to progression, an average 6 months)
- Explore Progression-Free Survival (PFS) of ISU104 or ISU104+Cetuximab(up to progression, an average 6 months)
- Determine Immunogenicity of ISU104(through the study completion, an average of 1 year)
- Explore Disease Control Rate (DCR) of ISU104 or ISU104+Cetuximab(up to progression, an average 6 months)
- Determine the Area Under the Curve (AUC) of ISU104(up to 12 weeks)
- Toxicity Evaluation(through the study completion, an average of 1 year)
- Determine the Peak Plasma Concentration (Cmax) of ISU104(up to 12 weeks)