A Study of Onartuzumab (MetMAb) Versus Placebo in Combination With Paclitaxel Plus Platinum in Patients With Squamous Non-Small Cell Lung Cancer

• Progression-free survival (tumor assessments according to RECIST criteria) [ Time Frame: up to approximately 32 months ] [ Designated as safety issue: No ]
• Progression-free survival: Subgroup of patients with Met diagnostic-positive squamous NSCLC [ Time Frame: up to approximately 32 months ] [ Designated as safety issue: No ]

• Overall survival [ Time Frame: up to approximately 32 months ] [ Designated as safety issue: No ]
• Overall response rate (tumor assessments according to RECIST criteria) [ Time Frame: up to approximately 32 months ] [ Designated as safety issue: No ]
• Duration of response (time from first documented objective response to disease progression) [ Time Frame: up to approximately 32 months ] [ Designated as safety issue: No ]
• Disease control rate (rate of partial response plus complete response plus stable disease for at least 6 weeks) [ Time Frame: up to approximately 32 months ] [ Designated as safety issue: No ]
• Safety: Incidence of adverse events [ Time Frame: up to approximately 32 months ] [ Designated as safety issue: No ]
• Pharmacokinetics: serum concentration (Cmin/Cmax) [ Time Frame: Pre- and post-dose on Day 1 of Cycles 1, 2 and 4 and up to 2 years ] [ Designated as safety issue: No ]
• Plasma concentrations of paclitaxel/platinum [ Time Frame: Pre- and post-dose on Day 1 of Cycles 1 and 4 ] [ Designated as safety issue: No ]
• Serum levels of anti-therapeutic antibodies (MetMAb ATAs) [ Time Frame: Pre-dose Day 1 of Cycles 1, 2 and 4 ] [ Designated as safety issue: No ]

• Overall survival [ Time Frame: up to approximately 32 months ] [ Designated as safety issue: No ]
• Overall response rate (tumor assessments according to RECIST criteria) [ Time Frame: up to approximately 32 months ] [ Designated as safety issue: No ]
• Duration of response (time from first documented objective response to disease progression) [ Time Frame: up to approximately 32 months ] [ Designated as safety issue: No ]
• Disease control rate (rate of partial response plus complete response plus stable disease for at least 6 weeks) [ Time Frame: up to approximately 32 months ] [ Designated as safety issue: No ]
• Safety: Incidence of adverse events [ Time Frame: up to approximately 32 months ] [ Designated as safety issue: No ]
• Pharmacokinetics: serum concetration (Cmin/Cmax) [ Time Frame: Pre- and post-dose on Day 1 of Cycles 1, 2 and 4 and up to 2 years ] [ Designated as safety issue: No ]
• Plasma concentrations of paclitaxel/platinum [ Time Frame: Pre- and post-dose on Day 1 of Cycles 1 and 4 ] [ Designated as safety issue: No ]
• Serum levels of anti-therapeutic antibodies (MetMAb ATAs) [ Time Frame: Pre-dose Day 1 of Cycles 1, 2 and 4 ] [ Designated as safety issue: No ]

This multicenter, randomized, double-blind, placebo-controlled study will evaluate the efficacy and safety of onartuzumab (MetMAb) in combination with paclitaxel plus platinum in patients with incurable Stage IIIB or Stage IV squamous non-small cell lung cancer (NSCLC). Patients will be randomized to receive either onartuzumab (MetMAb) 15 mg/kg iv or placebo on Day 1 of each 21-day cycle in combination with 4 cycles of paclitaxel 200 mg/m2 iv and platinum (carboplatin/cisplatin) iv on Day 1 of each 21-day cycle. Patients who have not progressed after 4 cycles will continue with either onartuzumab (MetMAb) or placebo as maintenance therapy until disease progression or unacceptable toxicity occurs.

• Drug: onartuzumab
  15 mg/kg iv, Day 1 of each 21-day cycle
  Other Name: MetMAb
• Drug: Placebo
  Matching onartuzumab (MetMAb) placebo iv, Day 1 of each 21-day cycle
• Drug: paclitaxel
  200 mg/m2 iv, Day 1 of each 21-day cycle, 4 cycles
• Drug: cisplatin/carboplatin
  standard dose iv, Day 1 of each 21-day cycle, 4 cycles

• Experimental: MetMAb+paclitaxel+platinum
  Interventions:

  • Drug: onartuzumab
  • Drug: paclitaxel
  • Drug: cisplatin/carboplatin
• Active Comparator: Placebo+paclitaxel+platinum
  Interventions:

  • Drug: Placebo
  • Drug: paclitaxel
  • Drug: cisplatin/carboplatin

Inclusion Criteria:

• Adult patients, >/= 18 years of age
• Histologically or cytologically confirmed Stage III B or Stage IV squamous non-small cell lung cancer (NSCLC)
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• No prior chemotherapy for squamous NSCLC
• Adequate tissue for central IHC assay of Met receptor, and EGFR testing if EGFR status is unknown
• Radiographic evidence of disease

Exclusion Criteria:

• Prior systemic treatment for Stage IIIB or IV squamous NSCLC
• NSCLC with histology classified as adenocarcinoma, large cell, mixed adenosquamous, or NSCLC not otherwise specified (NOS)
• Prior exposure to experimental treatment targeting either the 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
• Uncontrolled brain metastases and treatment by neurosurgical resection or brain biopsy within 4 weeks prior to Day 1 of Cycle 1
• History of another malignancy in the previous 3 years except for prior history of in situ cancer or basal or squamous cell skin cancer
• Pregnant or lactating women
• Uncontrolled diabetes
• Impaired bone marrow, liver or renal function as defined by protocol
• Significant history of cardiovascular disease
• Positive for HIV infection