A Study to Assess Biomarkers Impact on Participants Response to Erlotinib Treatment for First-line Non-Small Cell Lung Cancer With Endothelial Growth Factor Receptor (EGFR) Activating Mutations

Study Overview
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Brief Summary
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This open-label, single-arm, multi-center study will evaluate the progression-free survival in participants with histologically documented, advanced and/or metastatic chemotherapy naive, non-small cell lung cancer (NSCLC) with Epidermal Growth Factor Receptor (EGFR) positive mutations and receiving erlotinib treatment. The anticipated time on study treatment is until disease progression, unacceptable toxicity, withdrawal due to any reason or death.

Official Title
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Biomarkers Impact on the Response to Treatment With Erlotinib in First Line Non-small Cell Lung Cancer With EGFR Activating Mutations - BIOTEC

Conditions
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Carcinoma，Non-Small-Cell Lung

Intervention / Treatment
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* Drug: Erlotinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histological documented adenocarcinoma, locally advanced - Stage IIIB, metastatic - Stage IV or recurrent non-squamous NSCLC Activated EGFR mutation positive status (Exons 19 and 21) for treatment phase Eastern Cooperative Oncology Group (ECOG) performance status 0-1 Life expectancy greater than or equal to (≥) 12 weeks Evidence of disease with at least one measurable disease evaluation on Response Evaluation Criteria in Solid Tumors (RECIST) Adequate hematological , liver and renal function Exclusion Criteria: Known hypersensitivity to erlotinib or any of its excipients Squamous non-small cell or small cell tumors or absence of histological report Neoadjuvant/adjuvant chemotherapy within 6 months prior to enrollment Prior exposure to inhibitors of EGFR Prior chemotherapy or treatment with another systemic anti-cancer agent for the treatment of the participant's current stage of disease Any significant ophthalmologic abnormality, especially severe dry eye syndrome, keratoconjunctivitis sicca, Sjögren syndrome, severe exposure keratitis or any other disorder likely to increase the risk of corneal epithelial lesions Radical radiotherapy with curative intent within 28 days prior to enrollment Any active non-controlled systemic disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Erlotinib<br>Participants will receive 150 milligrams (mg) erlotinib orally daily until disease progression, unacceptable toxicity, withdrawal due to any reason or death. | Drug: Erlotinib<br>* Erlotinib 150 mg oral doses will be administered daily.<br>* Other names: Tarceva;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-Free Survival (PFS), as Assessed by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | PFS was the time from inclusion in the study to the date of first documented PD or death from any cause, whichever occurred first. Participants without event were censored at the date of the last tumor assessment where non-progression was documented. If a participant received a second anti-cancer therapy without prior documentation of disease progression, the participant was censored at the date of last tumor assessment before starting new chemotherapy. Analysis was performed using Kaplan-Meier method. PD was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. | Baseline up to approximately 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Disease Progression, as Assessed by Investigator Using RECIST v1.1 | Time to disease progression was defined as the time from baseline evaluation to the first date PD was recorded. Participants without progression were censored at the date of last tumor assessment where non-progression was documented. PD was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. | Baseline up to approximately 4 years | 
| Percentage of Participants With Complete Response (CR) And Partial Response (PR) as Assessed by the Investigator Using RECIST v1.1 | CR was defined as the disappearance of all target lesions, and PR was defined as at least a 30% decrease in the sum of the longest diameter compared to baseline. | Baseline up to approximately 4 years | 
| Percentage of Participants Who Were Alive One Year After Study Treatment Initiation |  | Year 1 | 
| Percentage of Participants by Localization of PD, as Assessed by Investigator Using RECIST v1.1 | PD was assessed using RECIST v1.1. PD was defined as at least a 20% increase in the sum of LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of 1 or more new lesions. Percentage of participants by localization of PD were reported. Localization included: Left lung inferior lobe; Para-aortic; Left lung upper lobe; Right lung inferior lobe; and Infracranial. | Baseline up to approximately 4 years | 
| Number of EGFR Positive Participants Classified Based on Smoking Status | Participants were asked: Have you smoked at least 100 cigarettes in your entire life? and Do you now smoke cigarettes every day, some days, or not at all? Responses were grouped into three categories: Current Smoker, Former Smoker, and Non-Smoker. Participants who reported smoking at least 100 cigarettes in their lifetime and who, at the time of survey, smoked either every day or some days were defined as 'Current smoker'. Participants who reported smoking at least 100 cigarettes in their lifetime and who, at the time of the survey, did not smoke at all were defined as 'Former smoker'. Participants who reported never having smoked 100 cigarettes were defined as 'Non-smoker'. | Day 1 | 
| Number of EGFR Positive Participants Classified Based on Type of EGFR Mutations | Participants with NSCLC have tumor associated with EGFR mutations. These mutations occur within EGFR Exons 18-21, which encodes a portion of the EGFR kinase domain. | Day 1 | 
| Percentage of Similar EGFR Mutations Between Matched Plasma and Tumor Tissue Samples |  | Baseline up to approximately 4 years |