Scribner and colleagues leveraged two platforms – an intact tumor cell immunization target discovery platform and a maytansine-based linker-drug platform – to identify cancer targets and develop ADCs against these targets. Antibodies to ADAM9 were generated with properties amenable to an ADC approach - among them, strong tumor-to-normal tissue binding differential and efficient internalization/processing by tumor cells. IMGC936, an ADC incorporating site-specific conjugation of DM21-C, a next-generation maytansine payload, was developed. IMGC936 exhibits potent antitumor activity in human CDX/PDX models and an acceptable safety profile in primates. The data supports initiation of a first-in-human study of IMGC936 in patients with solid tumors.

Active mutations in epidermal growth factor receptor (EGFR) are found in about 15% of Caucasian and 30–40% of Asian patients with advanced non-small-cell lung cancer (NSCLC). Currently there are no effective treatment options for NSCLC patients with osimertinib-resistant EGFR triple mutations. Here, Yong Du and coworkers report an...

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