MET inhibitors start on road to recovery: high-profile failures imperilled emerging anticancer MET inhibitors, but trials guided by a new biomarker are beginning to …

K Garber - Nature Reviews Drug Discovery, 2014 - go.gale.com
K Garber
Nature Reviews Drug Discovery, 2014go.gale.com
The failure of a Phase III lung cancer trial of the MET-specific antibody onartuzumab
shocked the community and dented hopes for an important anticancer drug class when
Genentech announced the results in March. Genentech halted the METLung trial early, after
an interim analysis showed that onartuzumab in combination with the epidermal growth
factor receptor (EGFR) inhibitor erlotinib did not provide any meaningful benefit over
erlotinib alone. ArQule's putative MET inhibitor tivantinib had failed 18 months earlier in a …
The failure of a Phase III lung cancer trial of the MET-specific antibody onartuzumab shocked the community and dented hopes for an important anticancer drug class when Genentech announced the results in March. Genentech halted the METLung trial early, after an interim analysis showed that onartuzumab in combination with the epidermal growth factor receptor (EGFR) inhibitor erlotinib did not provide any meaningful benefit over erlotinib alone. ArQule's putative MET inhibitor tivantinib had failed 18 months earlier in a similar Phase III lung cancer trial. The value of MET as a target in its most promising major indications, lung cancer and gastric cancer (where GlaxoSmithKline's foretinib failed in Phase II) seemed in doubt.
But this year's annual meeting of the American Society for Clinical Oncology (ASCO) signalled the return of MET as a viable target. Critics of Genentech's METLung trial described flaws in the firm's patient selection strategy, while several companies presented promising early-stage results using a better-performing biomarker.
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