Clinical Trials List
Protocol NumberI4C-MC-JTBB
NCT Number(ClinicalTrials.gov Identfier)NCT01897480
2013-07-01 - 2021-06-30
Phase II
Terminated5
ICD-10C34.90
Malignant neoplasm of unspecified part of unspecified bronchus or lung
A Randomized, Controlled Phase 2 Study Evaluating LY2875358 plus Erlotinib versus Erlotinib as First-Line Treatment in Metastatic Non–Small Cell Lung Cancer Patients with Activating EGFR Mutations Who Have Disease Control after an 8-Week Lead-In Treatment with Erlotinib
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Trial Applicant
ELI LILLY AND COMPANY(TAIWAN), INC.
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Sponsor
Eli Lilly and Company
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Trial scale
Multi-Regional Multi-Center
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Update
2025/08/20
Investigators and Locations
Co-Principal Investigator
- 蔡俊明 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- TSUNG -YING YANG Division of Thoracic Medicine
- 陳焜結 Division of Thoracic Medicine
- JENG-SEN TSENG Division of Thoracic Medicine
- KUO-HSUAN HSU Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Wen-Pin Su Division of Hematology & Oncology
- Shang-Yin Wu Division of Hematology & Oncology
- Yu-Min Yeh Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Co-Principal Investigator
- Chih-Yen Tu Division of Thoracic Medicine
- Wei-Chun Chen Division of Thoracic Medicine
- Chen Chia-Hung Division of Thoracic Medicine
- 陳鴻仁 Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
5 Stop recruiting
Co-Principal Investigator
- 徐偉勛 Division of Hematology & Oncology
- CHAO-CHI HO CHAO-CHI HO Division of General Internal Medicine
- Jih-Hsiang Lee Division of Hematology & Oncology
- 陳冠宇 Division of General Internal Medicine
- 林育麟 Division of Hematology & Oncology
- JIN-YUAN SHIH Division of General Internal Medicine
- 蔡子修 Division of General Internal Medicine
- Chia-Chi Lin Division of Hematology & Oncology
- Chong-Jen Yu Division of General Internal Medicine
- 廖唯昱 Division of General Internal Medicine
The Actual Total Number of Participants Enrolled
0 Stop recruiting
Condition/Disease
Non–Small Cell Lung Cancer
Objectives
The primary objective of this study is to compare PFS with LY2875358 plus erlotinib therapy with erlotinib monotherapy as first-line treatment in metastatic NSCLC patients with activating EGFR mutations who have disease control after an 8-week lead-in treatment with erlotinib monotherapy.
The secondary objectives of the study are as follows:
To compare efficacy variables
- Change in tumor size (CTS)
- Overall response rate (ORR)
- Duration of response (DoR)
- Time to progressive disease (TTPD)
- Disease control rate (DCR)
- Overall survival (OS)
To compare patient-reported symptoms and quality of life (QoL)
To characterize the safety and tolerability of LY2875358 plus erlotinib and compare it with erlotinib monotherapy.
To characterize and evaluate the pharmacokinetics of LY2875358 and erlotinib when administered in combination and compare them with erlotinib monotherapy.
To evaluate incidence and serum levels of antitherapeutic antibodies (ATAs) against LY2875358
The exploratory objectives for this study are as follows:
To evaluate tumor tissue and blood for biomarkers related to the MET signaling pathway or NSCLC biology (which may include but are not necessarily limited to MET protein expression, MET and EGFR amplification, HGF protein expression, confirmation of EGFR mutation [EGFRmt] status) and their potential association with the objectives of the study (including pharmacokinetic/pharmacodynamic [PK/PD] biomarker relationship).
Test Drug
LY2875358
Active Ingredient
humanized IgG4 mAb
Dosage Form
powder
Dosage
75
Endpoints
Criteria for Evaluation:
Primary Objective:
Progression-free survival (PFS): The time from the date of study randomization to the date of first observation of objective radiographic progression or death from any cause as defined by RECIST 1.1 (Eisenhauer et al. 2009)
Secondary Objectives:
Change in tumor size (CTS): The change in tumor size from baseline to the measurement with the smallest tumor size during the study.
Overall response rate (ORR): The proportion of patients who exhibit a confirmed CR or PR relative to baseline as defined by RECIST 1.1 (Eisenhauer et al. 2009)
Time to progressive disease (TTPD): The time from the date of study randomization to the date of first observation of objective progression.
Duration of response (DoR): The time from the date of first evidence of a confirmed CR or PR to the date of objective progression or the date of death due to any cause, whichever is earlier.
Disease control rate (DCR): The proportion of patients in the analysis population who exhibit SD or a confirmed CR or PR relative to baseline during the study; response is defined by RECIST 1.1 (Eisenhauer et al. 2009)
Overall survival (OS): The time from randomization until death for any reason .
Health Outcomes:
Patient symptoms and QoL will be assessed using the European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-LC13.
Safety:
Adverse events (AEs), serious adverse events (SAEs), physical examinations, vital sign measurements, clinical laboratory evaluations, treatment discontinuation due to toxicity, and safety will be evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Pharmacokinetics:
The parameters for erlotinib will include steady-state maximum and minimum concentration (Css,max and Css,min) and area under the concentration-time curve during the dosing interval at steady state (AUCτ,ss). The parameters for LY2875358 may include systemic clearance (CL), volume of distribution (V), Css,min, and target- mediated drug disposition (TMDD) model parameters, such as receptor mediated clearance, non–receptor-mediated clearance, volume of the central compartment, and volume of the peripheral compartment.
Exploratory Biomarkers:
Tumor tissue and blood samples will be collected and analyzed for exploratory biomarker related to the MET and EGFR signaling pathway or NSCLC biology. Tumor samples may be analyzed for, including, but not necessarily limited to MET protein expression, MET and EGFR amplification, HGF protein expression, and EGFR mutation (EGFRmt) status. Blood samples may be analyzed for, including, but not necessarily limited to, circulating levels of HGF and the extracellular cleaved domain of MET (MET ECD). Blood biomarker levels from baseline, leadin study period and the randomized study period may be compared. In addition the time course of blood biomarker levels during the study randomized study period and PK/PD biomarker relationship may be evaluated.
Primary Objective:
Progression-free survival (PFS): The time from the date of study randomization to the date of first observation of objective radiographic progression or death from any cause as defined by RECIST 1.1 (Eisenhauer et al. 2009)
Secondary Objectives:
Change in tumor size (CTS): The change in tumor size from baseline to the measurement with the smallest tumor size during the study.
Overall response rate (ORR): The proportion of patients who exhibit a confirmed CR or PR relative to baseline as defined by RECIST 1.1 (Eisenhauer et al. 2009)
Time to progressive disease (TTPD): The time from the date of study randomization to the date of first observation of objective progression.
Duration of response (DoR): The time from the date of first evidence of a confirmed CR or PR to the date of objective progression or the date of death due to any cause, whichever is earlier.
Disease control rate (DCR): The proportion of patients in the analysis population who exhibit SD or a confirmed CR or PR relative to baseline during the study; response is defined by RECIST 1.1 (Eisenhauer et al. 2009)
Overall survival (OS): The time from randomization until death for any reason .
Health Outcomes:
Patient symptoms and QoL will be assessed using the European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 and QLQ-LC13.
Safety:
Adverse events (AEs), serious adverse events (SAEs), physical examinations, vital sign measurements, clinical laboratory evaluations, treatment discontinuation due to toxicity, and safety will be evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.
Pharmacokinetics:
The parameters for erlotinib will include steady-state maximum and minimum concentration (Css,max and Css,min) and area under the concentration-time curve during the dosing interval at steady state (AUCτ,ss). The parameters for LY2875358 may include systemic clearance (CL), volume of distribution (V), Css,min, and target- mediated drug disposition (TMDD) model parameters, such as receptor mediated clearance, non–receptor-mediated clearance, volume of the central compartment, and volume of the peripheral compartment.
Exploratory Biomarkers:
Tumor tissue and blood samples will be collected and analyzed for exploratory biomarker related to the MET and EGFR signaling pathway or NSCLC biology. Tumor samples may be analyzed for, including, but not necessarily limited to MET protein expression, MET and EGFR amplification, HGF protein expression, and EGFR mutation (EGFRmt) status. Blood samples may be analyzed for, including, but not necessarily limited to, circulating levels of HGF and the extracellular cleaved domain of MET (MET ECD). Blood biomarker levels from baseline, leadin study period and the randomized study period may be compared. In addition the time course of blood biomarker levels during the study randomized study period and PK/PD biomarker relationship may be evaluated.
Inclution Criteria
Male and female patients ≥18 years of age with metastatic NSCLC (Stage IV), an activating EGFRmt, and an ECOG performance status ≤2 who had no previous line of systemic chemotherapy or molecular targeted therapy for treatment of NSCLC (first-line patients) will be eligible for this study. Only patients with no disease progression at the end of the erlotinib lead-in study period will proceed to the randomized part of study. Diagnosis
of NSCLC will be based on histopathologic or cytologic findings.
of NSCLC will be based on histopathologic or cytologic findings.
Exclusion Criteria
Exclusion Criteria
1. Are currently enrolled in, or discontinued within the last 30 days from, a
clinical trial involving an investigational product or nonapproved use of a
drug or device, or concurrently enrolled in any other type of medical research
judged not to be scientifically or medically compatible with this study.
2. Have previously completed or withdrawn from this study or any other study investigating LY2875358. (This exclusion criterion does not apply to patients who are rescreened prior to enrollment.)
3. Have a serious concomitant systemic disorder (eg, active infection including human immunodeficiency virus [HIV], or significant cardiac disease (eg, history of New York Heart Association class ≥3 disease, unstable angina, or myocardial infarction in 6 months prior to study drug administration) that, in the opinion of the investigator, would compromise the patient’s ability to adhere to the protocol.
4. Have interstitial pneumonia or interstitial fibrosis of the lung that, in the opinion of the investigator, could compromise the patient or the study treatment with erlotinib.
5. Have pleural effusion, pericardial fluid, or ascites requiring drainage every other week or more frequently.
6. Have a history of another malignancy except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years prior to the study.
7. Have any major surgery less than 2 weeks prior to initiation of study treatment.
8. Have any condition (eg, psychological, geographical.) that does not permit compliance with study and follow-up procedures or suggests that the patient is, in the investigator’s opinion, not an appropriate candidate for the study.
9. Are pregnant or lactating women.
1. Are currently enrolled in, or discontinued within the last 30 days from, a
clinical trial involving an investigational product or nonapproved use of a
drug or device, or concurrently enrolled in any other type of medical research
judged not to be scientifically or medically compatible with this study.
2. Have previously completed or withdrawn from this study or any other study investigating LY2875358. (This exclusion criterion does not apply to patients who are rescreened prior to enrollment.)
3. Have a serious concomitant systemic disorder (eg, active infection including human immunodeficiency virus [HIV], or significant cardiac disease (eg, history of New York Heart Association class ≥3 disease, unstable angina, or myocardial infarction in 6 months prior to study drug administration) that, in the opinion of the investigator, would compromise the patient’s ability to adhere to the protocol.
4. Have interstitial pneumonia or interstitial fibrosis of the lung that, in the opinion of the investigator, could compromise the patient or the study treatment with erlotinib.
5. Have pleural effusion, pericardial fluid, or ascites requiring drainage every other week or more frequently.
6. Have a history of another malignancy except for basal or squamous cell skin cancer and/or in situ carcinoma of the cervix, or other solid tumors treated curatively and without evidence of recurrence for at least 3 years prior to the study.
7. Have any major surgery less than 2 weeks prior to initiation of study treatment.
8. Have any condition (eg, psychological, geographical.) that does not permit compliance with study and follow-up procedures or suggests that the patient is, in the investigator’s opinion, not an appropriate candidate for the study.
9. Are pregnant or lactating women.
The Estimated Number of Participants
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Taiwan
25 participants
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Global
150 participants
