Pfizer’s first pivotal readout for sigvotatug vedotin (SV, an antibody-drug conjugate acquired via Seagen) missed the overall survival primary endpoint in its Phase 3 SigVie-002 trial in advanced, metastatic non-squamous NSCLC. The ADC did not achieve statistical significance versus docetaxel. Pfizer is continuing work based on subgroup signals, and the company also pointed to ongoing combination efforts, including a Keytruda-based Phase 3 study. Still, the failure marks another clinical setback for Pfizer’s ADC pipeline, which has been under pressure following the Seagen acquisition. Analytically, the trial’s OS miss introduces additional uncertainty around the ADC’s target biology and linker-payload performance, particularly given prior reporting that integrin beta-6 expression response relationships were not clearly established. The company characterized the population as historically difficult to treat and said more work is needed, leaving open a re-positioning risk for future ADC programs in NSCLC.