The MetLUNG study: A randomized, double-blind, phase III study of onartuzumab (MetMAb) plus erlotinib versus placebo plus erlotinib in patients with advanced, MET-positive non-small cell lung cancer (NSCLC).

TPS7616 Background: Increased Met signaling is associated with poor prognosis in NSCLC and can result in acquired resistance to epidermal growth factor receptor (EGFR)-targeted drugs in EGFR-mutant lung tumors. Onartuzumab (MetMAb) is a humanized monovalent monoclonal antibody that binds to Met with high specificity, preventing HGF ligand binding and blocking downstream signaling. Onartuzumab has shown anticancer activity in preclinical studies (Merchant et al. AACR 2008:Abstr. 1336) and in a phase I study of patients with advanced solid tumors (Moss et al. Ann Oncol 2010;21(Suppl. 8):Abstr. 504P). In a phase II study, patients with Met-positive tumors (≥50% of tumor cells stain 2+ or 3+ intensity by IHC) (Met Dx+) who received onartuzumab + erlotinib had nearly twofold reduction in the risk of disease progression and threefold reduction in the risk of death compared with erlotinib alone (Spigel et al. J Clin Oncol 2011;29(Suppl.):Abstr. 7505). An increased incidence of peripheral edema was observed in patients treated with onartuzumab. Methods: This is a randomized, phase III, multicenter, double-blind, placebo-controlled study. Adults with Met Dx+ tumors who failed at least 1 but no more than 2 prior lines of platinum-based chemotherapy for advanced NSCLC are eligible. Around 480 patients will receive (1:1) erlotinib (150 mg PO daily) + placebo or onartuzumab (15 mg/kg IV Q3W) until disease progression, unacceptable toxicity, patient/physician decision to discontinue, or death. Patients are stratified for Met expression (2+ vs 3+), prior lines of therapy (1 vs 2), histology (squamous vs nonsquamous) and EGFR-activating mutation status (yes vs no). The primary endpoint is OS. Secondary endpoints include PFS, response rates, safety, patient-reported outcomes, and PK. An IDMC will monitor safety every 6 months after the 1st patient is enrolled and evaluate 1 interim analysis when ~67% of the total OS events have occurred. This study is open for accrual; further details can be found on ClinicalTrials.gov (NCT01456325).