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

• ClinicalTrials.gov Identifier: NCT01496742
• Recruitment Status: Completed
• First Posted: December 21, 2011
• Last Update Posted: September 23, 2016
• Sponsor: Genentech, Inc.
• Information provided by (Responsible Party): Genentech, Inc.

Tracking Information

• First Submitted Date: December 19, 2011
• First Posted Date: December 21, 2011
• Last Update Posted Date: September 23, 2016
• Study Start Date: April 2012
• Actual Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 19, 2011)

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 19, 2011)

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

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double; Primary Purpose: Treatment
• Condition: Non-Squamous Non-Small Cell Lung Cancer

Intervention

• Drug: Placebo
  Matching RO5490258 (MetMAb) placebo iv, Day 1 of each 21-day cycle
• Drug: RO5490258
  15 mg/kg iv, Day 1 of each 21-day cycle
  Other Name: MetMAb
• Drug: bevacizumab [Avastin]
  15 mg/kg iv, Day 1 of each 21-day cycle
• 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: pemetrexed
  500 mg/m2, Day 1 of each 21-day cycle

Study Arms

• Experimental: Bevacizumab+MetMAb
  Interventions:

  • Drug: RO5490258
  • Drug: bevacizumab [Avastin]
  • Drug: cisplatin/carboplatin
  • Drug: paclitaxel
• Active Comparator: Bevacizumab+Placebo
  Interventions:

  • Drug: Placebo
  • Drug: bevacizumab [Avastin]
  • Drug: cisplatin/carboplatin
  • Drug: paclitaxel
• Experimental: Pemetrexed+MetMAb
  Interventions:

  • Drug: RO5490258
  • Drug: cisplatin/carboplatin
  • Drug: pemetrexed
• Active Comparator: Pemetrexed+Placebo
  Interventions:

  • Drug: Placebo
  • Drug: cisplatin/carboplatin
  • Drug: pemetrexed

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 21, 2016): 259
• Original Estimated Enrollment (submitted: December 19, 2011): 260
• Actual Study Completion Date: November 2015
• Actual Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, France, Germany, Israel, Italy, Latvia, Malaysia, Mexico, Philippines, Spain, Taiwan, United Kingdom, United States
• Removed Location Countries: Brazil, Portugal, Russian Federation

Administrative Information

• NCT Number: NCT01496742
• Other Study ID Numbers: GO27821; 2011-003719-42 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Genentech, Inc.
• Study Sponsor: Genentech, Inc.
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Genentech, Inc.

• PRS Account: Genentech, Inc.
• Verification Date: September 2016