Metmab

Disease Area: Lung Cancer

About MetMab:

Onartuzumab, also known as MetMab, was designed to block the MET protein, which is overproduced in half of cases of non-small cell lung cancer (NSCLC). March 3, 2014 Genenteh announced that it would stop the Phase III METLung study of onartuzumab due to a “lack of meaningful clinical efficacy.”

What We Learned:

Albeit the disappointing outcome of this trial, for both Genentech and those affected by lung cancer, our scientists were able to perform a deep analysis on what did not work to help our future programs.

Key lessons learned from the MetMAb program:

When a biomarker hypothesis is evaluated in a trial, its association with outcome should be treated cautiously until confirmed in a second study.

Availability of data from more than one clinical study proximal to the LIP decision would allow better estimation of program risk, but comes at additional cost.

Line extensions for early programs carry additional risk (compared to validated programs), until the original proof of concept is confirmed

For broad programs there is a correlated risk that should be assessed to fully understand potential risk-adjusted value of a program

What other programs this has impacted:

When an IHC CDx is used in a trial to prospectively select or stratify patients, a prevalence monitoring plan should be established prior to study start in order to monitor drift and pathologist performance. This was not done in MetMab but it is now performed across trials.