Roche today acknowledged its second failed pivotal clinical trial this year by halting its Phase III METLung study of its MetMab (onartuzumab) in combination with Astellas Pharma’s Tarceva (erlotinib) for previously treated, advanced non-small cell lung cancer (NSCLC) whose tumors were identified as MET-positive.
The halt follows the recommendation of the study’s independent data monitoring committee, which cited what Roche called “a lack of clinically meaningful efficacy” following a pre-specified interim analysis. The company said it would present its data at an unspecified “forthcoming medical meeting”
"These results are disappointing because new options are needed for patients with lung cancer, the most common and deadly cancer worldwide,” Sandra Horning, M.D., CMO and head of global product development. "We remain committed to helping patients with lung cancer and are studying several investigational medicines in this disease.”
Roche did not immediately terminate MetMab, saying instead it was “evaluating the implications of the METLung study results across the ongoing onartuzumab clinical program.”
That was the company’s same stance in January, when it disclosed that two Phase III trials of bitopertin (RG1678) in adults with persistent, predominant negative symptoms of schizophrenia failed to meet their primary endpoints. Adding bitopertin to antipsychotic therapy did not significantly reduce the mean change from baseline in the PANSS negative symptoms factor score at 24 weeks compared to placebo, as measured by the positive and negative symptom scale (PANSS).
In the case of MetMab, the Phase III METLung trial sought to assess whether the investigational monovalent (one-armed) monoclonal antibody could halt tumor growth and metastasis by targeting the receptor for MET a protein found on the surface of cells. When MET binds to Hepatocyte Growth Factor (HGF), a protein also called "Scatter Factor," the MET proteins dimerise, triggering a signaling cascade that tells cells to grow, divide, and spread to other parts of the body.
The primary endpoint for METLung was overall survival up to approximately 40 months, with secondary endpoints including progression-free survival, objective response rate and safety profile. A total 499 patients were randomized to receive 150 mg of Tarceva taken daily plus either intravenous 15 mg/kg of onartuzumab every three weeks, or intravenous placebo every three weeks. The METLung study included a companion diagnostic immunohistochemistry test co-developed with Roche’s Ventana Medical Systems.
Overall adverse event rates were generally similar between both groups, Roche said.