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

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

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.

Study Overview

• Status: Completed
• Conditions: Non-Squamous Non-Small Cell Lung Cancer
• Intervention / Treatment: Drug: erlotinib; Drug: onartuzumab; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 3

Contacts and Locations

Study Locations

• France
  • Caen, France, 14076
  • Lyon, France, 69373
  • Nantes, France, 44805
• Germany
  • Grosshansdorf, Germany, 22927
  • Oldenburg, Germany, 26121
  • Villingen-Schwenningen, Germany, 78052
• Japan
  • Ehime, Japan, 791-0280
  • Okayama, Japan, 700-8558
  • Yamaguchi, Japan, 755-0241
• Korea, Republic of
  • Gwangju, Korea, Republic of, 501-757
  • Suwon-si,, Korea, Republic of, 442-723
• Malaysia
  • Tanjung Bungah, Malaysia, 11200
• Spain
  • Barcelona, Spain, 08035
  • Barcelona, Spain, 08025
  • Madrid, Spain, 28007
  • Madrid, Spain, 28222
  • Madrid, Spain, 28050
• Taiwan
  • Taichung, Taiwan, 40447
  • Taipei, Taiwan, 100
  • Taipei, Taiwan, 00112
• United States
  • California
    • Bakersfield, California, United States, 93309
    • Fullerton, California, United States, 92835
    • Long Beach, California, United States, 90813
    • Los Angeles, California, United States, 90095
    • Los Angeles, California, United States, 90095-1772
    • San Luis Obispo, California, United States, 93454
  • Florida
    • Fort Myers, Florida, United States, 33905
    • Orlando, Florida, United States, 32803
    • Saint Petersburg, Florida, United States, 33705
  • Illinois
    • Chicago, Illinois, United States, 60637
  • Louisiana
    • Marrero, Louisiana, United States, 70072
    • Metairie, Louisiana, United States, 70006
  • Missouri
    • St. Louis, Missouri, United States, 63110
  • Ohio
    • Canton, Ohio, United States, 44718
  • Tennessee
    • Nashville, Tennessee, United States, 37203

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	approximately 3 years
Safety: Incidence of adverse events	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
Pharmacokinetics: Area under the concentration-time curve (AUC)	Day 1 Cycles 1, 2 and 4

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: June 25, 2013
• First Submitted That Met QC Criteria: June 25, 2013
• First Posted (Estimate): June 27, 2013

Study Record Updates

• Last Update Posted (Estimate): November 2, 2016
• Last Update Submitted That Met QC Criteria: November 1, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• Other Study ID Numbers: GO28758; 2013-000868-29 (EudraCT Number)