A Study of Onartuzumab (MetMAb) in Combination With Bevacizumab (Avastin) Plus Platinum And Paclitaxel or With Pemetrexed Plus Platinum in Patients With Non-Squamous Non-Small Cell Lung Cancer

A Randomized, Phase II, Multicenter, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Metmab Vs. Placebo in Combination With Either Bevacizumab + Platinum + Paclitaxel or Pemetrexed + Platinum in Patients With Untreated Stage IIIb or IV Non-Squamous NSCLC

This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of RO5490258 (MetMab) in combination with either of two backbone chemotherapy regimens in the first-line setting in patients with incurable Stage IIIB or IV non-squamous non-small cell lung cancer. In Cohort 1, patients will be randomized to receive 4 cycles of bevacizumab (Avastin) 15 mg/kg iv, paclitaxel 200 mg/m2 iv, platinum (cisplatin/carboplatin) iv plus either MetMab 15 mg/kg iv or placebo on Day 1 of each 21-day cycle. In Cohort 2, patients will be randomized to receive pemetrexed 500 mg/m2 iv, platinum (cisplatin/carboplatin) iv plus either MetMAb 15 mg/m2 iv or placebo on Day 1 of each 21-day cycle. Patients who have not progressed after 4 cycles will be offered maintenance therapy with their assigned treatment of bevacizumab plus either MetMAb or placebo (Cohort 1) or pemetrexed plus either MetMAb or placebo (Cohort 2). 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: cisplatin/carboplatin; Drug: paclitaxel; Drug: RO5490258; Drug: bevacizumab [Avastin]; Drug: Placebo; Drug: pemetrexed

• Study Type: Interventional
• Enrollment (Actual): 259
• Phase: Phase 2

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1426ANZ
  • La Rioja, Argentina, F5300COE
  • Santa Rosa, Argentina, L6304BOC
• France
  • Grenoble, France, 38043
  • Paris, France, 75674
  • Paris, France, 75230
  • Rennes, France, 35033
• Germany
  • Göttingen, Germany, 37075
  • Halle (Saale), Germany, 06120
  • Immenhausen, Germany, 34376
  • München, Germany, 81925
  • Münster, Germany, 48149
• Israel
  • Afula, Israel, 18101
  • Ashkelon, Israel, 78278
  • Holon, Israel, 58100
  • Tel Aviv, Israel, 6423906
  • Zerifin, Israel, 6093000
• Italy
  • Campania
    • Avellino, Campania, Italy, 83100
  • Friuli-Venezia Giulia
    • Udine, Friuli-Venezia Giulia, Italy, 33100
  • Lazio
    • Roma, Lazio, Italy, 00149
  • Lombardia
    • Cremona, Lombardia, Italy, 26100
    • Milano, Lombardia, Italy, 20133
  • Piemonte
    • Orbassano, Piemonte, Italy, 10043
• Latvia
  • Daugavpils, Latvia, 5417
  • Liepaja, Latvia, LV 3401
  • Riga, Latvia, LV-1002
  • Riga, Latvia, LV 1079
• Malaysia
  • Kuala Lumpur, Malaysia, 56000
  • Negeri Sembilan, Malaysia, 71800
  • Penang, Malaysia, 10050
  • Pulau Pinang, Malaysia, 11600
  • Tanjung Bungah, Malaysia, 11200
• Mexico
  • Aguascalientes, Mexico, 20234
  • Chihuahua, Mexico, 31000
  • Leon, Mexico, 37150
• Philippines
  • CEBU City, Philippines, 6000
  • Davao City, Philippines, 8000
  • Pasig City, Philippines, 1605
  • Quezon City, Philippines, 1114
  • Quezon City, Philippines, 1104
• Spain
  • Barcelona, Spain, 08036
  • Madrid, Spain, 28007
  • Madrid, Spain, 28050
  • Zaragoza, Spain, 50009
  • Navarra
    • Pamplona, Navarra, Spain, 31008
• Taiwan
  • Kaohsiung, Taiwan, 807
  • Taichung, Taiwan, 40705
  • Tainan, Taiwan, 704
  • Taipei, Taiwan, 100
  • Taipei, Taiwan, 00112
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
  • Birmingham, United Kingdom, B9 5SS
  • Bournemouth, United Kingdom, BH7 7DW
  • Leeds, United Kingdom, LS9 7TF
  • Manchester, United Kingdom, M23 9QZ
• United States
  • Alabama
    • Huntsville, Alabama, United States, 35805
  • Arizona
    • Scottsdale, Arizona, United States, 85259
  • California
    • Bakersfield, California, United States, 93309
    • Fullerton, California, United States, 92835
    • Los Angeles, California, United States, 90024
    • Los Angeles, California, United States, 90095-1772
    • Northridge, California, United States, 91328
    • San Luis Obispo, California, United States, 93454
    • Santa Barbara, California, United States, 93105
    • Stanford, California, United States, 94305-5820
  • Colorado
    • Grand Junction, Colorado, United States, 81502-1628
  • Florida
    • Boynton Beach, Florida, United States, 33435
    • Hollywood, Florida, United States, 33021
    • Orlando, Florida, United States, 32804
  • Georgia
    • Lawrenceville, Georgia, United States, 30045
    • Marietta, Georgia, United States, 30060
  • Illinois
    • Harvey, Illinois, United States, 60426
  • Indiana
    • Fort Wayne, Indiana, United States, 46815
    • Fort Wayne, Indiana, United States, 46845
    • Indianapolis, Indiana, United States, 46260
    • Muncie, Indiana, United States, 47303
  • Louisiana
    • Metairie, Louisiana, United States, 70006
  • Minnesota
    • Minneapolis, Minnesota, United States, 55454
  • Nevada
    • Las Vegas, Nevada, United States, 89148
  • New York
    • New York, New York, United States, 10016
  • North Carolina
    • Hickory, North Carolina, United States, 28602
  • Ohio
    • Cleveland, Ohio, United States, 44195
    • Columbus, Ohio, United States, 43215
    • Middletown, Ohio, United States, 45042
  • Oregon
    • Bend, Oregon, United States, 97701
    • Portland, Oregon, United States, 97239
  • Washington
    • Seattle, Washington, United States, 98195

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 patients, >/= 18 years of age
• Histologically or cytologically confirmed Stage IIIB or Stage IV non-squamous non-small cell lung cancer (NSCLC)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• For patients who received prior adjuvant chemotherapy or chemoradiotherapy: a treatment-free interval of at least 12 months since last chemotherapy or chemoradiotherapy cycle
• Adequate tissue for central immunohistochemical (IHC) assay of Met receptor, and epidermal growth factor receptor (EGFR) testing if EGFR status is unknown
• Radiographic evidence of disease

Exclusion Criteria:

• Prior systemic treatment for Stage IIIB or IV non-squamous NSCLC
• Evidence of mixed NSCLC with a predominance of the squamous cell type
• Prior exposure to experimental treatment targeting either the hepatocyte growth factor (HGF) or Met pathway
• Patients with tumors confirmed to have EGFR-activating mutations who are suitable for anti-EGFR therapy (e.g. gefitinib or erlotinib), as determined by the investigator, unless that treatment is unavailable or refused by the patient
• Known central nervous system (CNS) disease, other than stable, treated brain metastases
• History of another malignancy in the previous 3 years, except for history of in situ cancer that was treated surgically with curative intent, localized prostate cancer that has been treated surgically with curative intent, or basal or squamous cell skin cancer
• Uncontrolled diabetes
• Pregnant or lactating women
• Impaired bone marrow, liver or renal function (as defined by protocol)
• Significant history of cardiovascular disease
• Positive for HIV infection

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Bevacizumab+MetMAb	Drug: cisplatin/carboplatin; standard dose iv, Day 1 of each 21-day cycle, 4 cycles; Drug: paclitaxel; 200 mg/m2 iv, Day 1 of each 21-day cycle, 4 cycles; Drug: RO5490258; 15 mg/kg iv, Day 1 of each 21-day cycle; Other Names: MetMAb; Drug: bevacizumab [Avastin]; 15 mg/kg iv, Day 1 of each 21-day cycle
Active Comparator: Bevacizumab+Placebo	Drug: cisplatin/carboplatin; standard dose iv, Day 1 of each 21-day cycle, 4 cycles; Drug: paclitaxel; 200 mg/m2 iv, Day 1 of each 21-day cycle, 4 cycles; Drug: bevacizumab [Avastin]; 15 mg/kg iv, Day 1 of each 21-day cycle; Drug: Placebo; Matching RO5490258 (MetMAb) placebo iv, Day 1 of each 21-day cycle
Experimental: Pemetrexed+MetMAb	Drug: cisplatin/carboplatin; standard dose iv, Day 1 of each 21-day cycle, 4 cycles; Drug: RO5490258; 15 mg/kg iv, Day 1 of each 21-day cycle; Other Names: MetMAb; Drug: pemetrexed; 500 mg/m2, Day 1 of each 21-day cycle
Active Comparator: Pemetrexed+Placebo	Drug: cisplatin/carboplatin; standard dose iv, Day 1 of each 21-day cycle, 4 cycles; Drug: Placebo; Matching RO5490258 (MetMAb) placebo iv, Day 1 of each 21-day cycle; Drug: pemetrexed; 500 mg/m2, Day 1 of each 21-day cycle

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Progression-free survival (tumor assessments according to RECIST criteria)	up to approximately 23 months
Progression-free survival: Subgroup of patients with Met diagnostic positive tumors	up to approximately 23 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Serum levels of anti-therapeutic antibodies (MetMAb ATAs)	Pre-dose Day 1 of Cycles 1, 2 and 4
Overall survival	up to approximately 23 months
Overall response rate (tumor assessments according to RECIST criteria)	up to approximately 23 months
Duration of response (time from first documented objective response to disease progression)	up to approximately 23 months
Disease control rate (rate of partial response plus complete response plus stable disease for at least 6 weeks)	up to approximately 23 months
Safety: Incidence of adverse events	up to approximately 23 months
Pharmacokinetics: serum concentration (Cmin/Cmax)	Pre- and post-dose on Day 1 of Cycles 1, 2 and 4 and at study termination
Serum concentrations of bevacizumab/paclitaxel/pemetrexed/platinum in combination with MetMAb	Pre- and post-dose on Day 1 of Cycles 1 and 4

Collaborators and Investigators

• Sponsor: Genentech, Inc.

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): November 1, 2015
• Study Completion (Actual): November 1, 2015

Study Registration Dates

• First Submitted: December 19, 2011
• First Submitted That Met QC Criteria: December 19, 2011
• First Posted (Estimate): December 21, 2011

Study Record Updates

• Last Update Posted (Estimate): September 23, 2016
• Last Update Submitted That Met QC Criteria: September 21, 2016
• Last Verified: September 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Folic Acid Antagonists; Carboplatin; Paclitaxel; Bevacizumab; Pemetrexed
• Other Study ID Numbers: GO27821; 2011-003719-42 (EudraCT Number)