GATSBY

GATSBY was an adaptive phase 2/3 trial in HER2-positive advanced gastric or gastro-oesophageal junction adenocarcinoma that had progressed during or after first-line therapy. Stage 1 randomised patients to two dose schedules of trastuzumab emtansine or to a taxane chosen by the investigator; the 2.4 mg/kg weekly schedule was carried into stage 2 against taxane alone.

Trastuzumab emtansine did not improve overall survival over taxane, the primary endpoint, and the trial was stopped. Together with the earlier failure of lapatinib in this setting, GATSBY showed that HER2 loss and heterogeneity after trastuzumab make second-line HER2 targeting in gastric cancer harder than in breast cancer; the later success of trastuzumab deruxtecan in DESTINY-Gastric01 came from a payload that also kills neighbouring HER2-negative cells.