A Study of Onartuzumab in Combination With Erlotinib in Patients With MET-Positive Stage IIIB or IV Non-Small Cell Lung Cancer Carrying an Activating Epidermal Growth Factor Receptor (EGFR) Mutation

Study Overview
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Brief Summary
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This multicenter, randomized, double-blind, placebo-controlled study will evaluate the safety and efficacy of onartuzumab in combination with erlotinib in patients with previously untreated, unresectable stage IIIB or IV non-small cell lung cancer identified to carry and activating EGFR mutation and MET-positive. Patients will be randomized to receive either onartuzumab 15 mg/kg intravenously every 3 weeks in combination with erlotinib 150 mg orally daily or placebo in combination with erlotinib. Anticipated time on study treatment is until disease progression or unacceptable toxicity occurs.

Official Title
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A Randomized, Phase III, Multicenter, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Onartuzumab in Combination With Erlotinib as First-Line Treatment for Patients With MET-Positive Unresectable Stage IIIb or IV Non-Small Cell Lung Cancer (NSCLC) Carrying an Activating EGFR Mutation

Conditions
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Non-Squamous Non-Small Cell Lung Cancer

Intervention / Treatment
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* Drug: erlotinib
* Drug: onartuzumab
* Drug: placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patient, >/= 18 years of age Histologically confirmed, unresectable Stage IIIB or IV non-small cell lung cancer (NSCLC) No prior treatment for unresectable Stage IIIB or IV NSCLC Measurable radiographic evidence of disease according to RECIST v1.1 Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 Exclusion Criteria: Prior exposure to agents targeting either the Hepatocyte Growth Factor (HGF) or MET pathway Exposure to an investigational or marketed agent that can act by EGFR inhibition Pleural effusion, pericardial fluid, or ascites requiring drainage every other week or more frequently Brain metastasis or spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated central nervous system (CNS) metastases or spinal cord compression without evidence of clinically stable disease for >/=4 days. Note: Patients with treated CNS metastases who are asymptomatic and on a stable dose of corticosteroids for >/= 14 days prior to randomization are eligible. History of another malignancy in the previous 5 years, unless cured by surgery alone and continuously disease-free Radiographically evident interstitial lung disease , concurrent infection, or a history of any of these conditions Inadequate hematologic, biochemical, and organ function Pregnant or lactating women Life expectancy of < 12 weeks Receipt of an investigational drug within 28 days prior to initiation of study treatment

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Onartuzumab + Erlotinib<br> | Drug: erlotinib<br>* 150 mg orally daily<br>Drug: onartuzumab<br>* 15 mg/kg IV every 3 weeks<br>|
| Active Comparator: Placebo + Erlotinib<br> | Drug: erlotinib<br>* 150 mg orally daily<br>Drug: placebo<br>* IV every 3 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival (investigator-assessed according to RECIST v1.1) |  | approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | approximately 3 years | 
| Overall response rate |  | approximately 3 years | 
| Time to deterioration (>/= 10 points [transformed score] from baseline) in patient-reported lung cancer symptoms |  | approximately 3 years | 
| Patient reported outcomes: HRQoL/EORTC QLC-C30/EORTC QLQ-LC31 questionnaires |  | approximately 3 years | 
| Safety: Incidence of adverse events |  | approximately 3 years | 
| Pharmacokinetics: Area under the concentration-time curve (AUC) |  | Day 1 Cycles 1, 2 and 4 |