Sigvotatug vedotin just missed overall survival in second-line NSCLC. The instinct is to read it as a Pfizer problem. It is closer to a setting problem.

The all-comer survival play has failed for ADCs here. No ADC has beaten chemotherapy on overall survival in a broad, unselected second-line population. Sigvotatug vedotin, datopotamab deruxtecan, and sacituzumab govitecan all missed against docetaxel, three different payloads, two of them TROP2-directed.

The wins are all biomarker-selected. Three ADCs are approved in pretreated NSCLC on response rate: Enhertu in HER2-mutant, Emrelis in c-Met-high, Datroway in EGFR-mutant. And the one ADC to actually beat docetaxel on survival, sacituzumab tirumotecan, did it in EGFR-mutant disease, not all-comers, and so far only in China. Even there it is mixed, patritumab deruxtecan also missed overall survival in EGFR-mutant disease.

So sigvotatug’s miss is not the Seagen platform breaking. It is the latest sign that in second-line lung cancer, ADCs that chase the whole population on survival lose. Every win so far has been biomarker-selected.