A phase III trial of Roche’s cancer prospect onartuzumab has been abandoned after the drug failed to show efficacy.
The METLung study looked at the effect of adding onartuzumab to Tarceva (erlotinib) as a second- or third-line therapy for patients with non-small cell lung cancer (NSCLC), but use of the drugs in combination was unable to demonstrate any “clinically meaningful efficacy” compared to Tarceva alone.
The drug is an inhibitor of c-Met, a tyrosine kinase over-expressed on the cell surface of multiple tumour types which contributes to cellular proliferation, invasion and survival and has also been linked to poor prognosis in many cancer types. It acts as a receptor that binds to another protein called hepatocyte growth factor (HGF), also known as scatter factor.
Onartuzumab, which is being developed under the provisional name of MetMAb, has also failed in a late-stage trial involving triple-negative breast cancer, although Roche had previously cautioned against drawing any conclusions about the potential of the drug in that study as it contained a very low number of c-MET-positive patients.
NSCLC was considered the most promising indication for onartuzumab, and Roche had indicated that positive results in the METLung study would have enabled it to move ahead with a regulatory filing in the US.
The failure to show a clinical benefit is somewhat surprising given impressive phase II data and the fact that Roche recently started phase III trials of the drug as a first-line therapy in both squamous and non-squamous NSCLC.
The drug remains in trials for other cancer indications, including colorectal and gastric cancer where it has reached phase II testing.
In a statement, Roche said it is evaluating the implications of the METLung study results across the entire onartuzumab clinical programme.
“These results are disappointing because new options are needed for patients with lung cancer, the most common and deadly cancer worldwide,” commented Sandra Horning, Roche’s chief medical officer.
It remains to be seen whether the failed study has implications for other c-MET inhibitors in clinical trials, although the class has had other notable casualties, including ArQule’s tivantinib (partnered with Daiichi) which failed an NSCLC trial in 2012 and was also ineffective in a phase II colorectal cancer study.
One c-MET inhibitor has reached the market – Exelixis’ Cometriq (cabozantinib) for thyroid cancer – although this has a dual activity and also inhibits VEGFR2. Exelixis is developing a similar molecule with combined activity called foretinib (XL880), which is partnered with GlaxoSmithKline and is in a phase I/II trial in triple-negative breast cancer.
Meanwhile, Amgen has a monoclonal antibody that inhibits the action HGF/scatter factor – called rilotumumab – in phase III trials for gastric cancer. That drug was resurrected after being suspended from development after a biomarker analysis, which teased out data on MET-positive patients.