Pfizer’s first ADC flowing from its 2023 Seagen acquisition, sigvotatug vedotin (SV), failed to reach statistical significance on overall survival in a Phase 3 non-small-cell lung cancer (NSCLC) study. The ADC did not outperform docetaxel in the overall population. In Pfizer’s SigmaV-002 study, results showed a “stronger trend” in patients who received only one prior line of systemic therapy, while no clear integrin beta-6 expression-response relationship emerged. Pfizer framed the target population as historically difficult to treat and said it will continue efforts based on subgroup signals and an ongoing Phase 3 Keytruda combination program. The outcome highlights how ADC programs can encounter sharp efficacy hurdles even when earlier signals justify progression—raising the bar for target validation, patient selection, and mechanism-aligned combinations in late-stage lung cancer trials.