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

Phase 2

Completed

Interventions: Drug: cisplatin/carboplatin
Drug: Placebo
Drug: onartuzumab
Drug: paclitaxel

Brief Summary: 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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
MetMAb+paclitaxel+platinum	cisplatin/carboplatin	-
Placebo+paclitaxel+platinum	paclitaxel	-
Placebo+paclitaxel+platinum	cisplatin/carboplatin	-
Placebo+paclitaxel+platinum	Placebo	-
MetMAb+paclitaxel+platinum	paclitaxel	-
MetMAb+paclitaxel+platinum	onartuzumab	-

Primary Outcome Measures

Name	Time	Method
Progression-free survival (tumor assessments according to RECIST criteria)	up to approximately 32 months
Progression-free survival: Subgroup of patients with Met diagnostic-positive squamous NSCLC	up to approximately 32 months

Secondary Outcome Measures

Name	Time	Method
Overall survival	up to approximately 32 months
Overall response rate (tumor assessments according to RECIST criteria)	up to approximately 32 months
Duration of response (time from first documented objective response to disease progression)	up to approximately 32 months
Disease control rate (rate of partial response plus complete response plus stable disease for at least 6 weeks)	up to approximately 32 months
Serum levels of anti-therapeutic antibodies (MetMAb ATAs)	Pre-dose Day 1 of Cycles 1, 2 and 4
Safety: Incidence of adverse events	up to approximately 32 months
Pharmacokinetics: serum concentration (Cmin/Cmax)	Pre- and post-dose on Day 1 of Cycles 1, 2 and 4 and up to 2 years
Plasma concentrations of paclitaxel/platinum	Pre- and post-dose on Day 1 of Cycles 1 and 4