Sigvotatug vedotin (ITGB6 vedotin ADC) + pembrolizumab drives 50% cORR in 1L aNSCLC across PD-L1

Sigvotatug vedotin (SV; SGN-B6A) is an investigational integrin beta-6 (ITGB6)–directed antibody–drug conjugate using a vedotin (MMAE) microtubule-inhibitor payload, here combined with pembrolizumab (SV 1.8mg/kg IV Q2W + pembrolizumab 400mg IV Q6W) in the open-label Phase 1 SGNB6A-001 dose-expansion cohorts (NCT04389632) in treatment-naive locally advanced/unresectable or metastatic NSCLC (and a separate HNSCC cohort). In the aNSCLC expansion cohort (median follow-up 10.6 months), confirmed ORR was 50% in PD-L1 TPS <1% (n=10) and 50% in PD-L1 TPS ≥1% (n=18), including 80% cORR in PD-L1 TPS ≥50% (n=5; plus one additional PR pending confirmation); this sits above typical pembrolizumab monotherapy ORR (45% in KEYNOTE-024 for TPS ≥50%) and is in the ballpark of chemo-IO ORR (48% in KEYNOTE-189, albeit in nonsquamous). Safety across 71 treated patients (37 aNSCLC, 33 HNSCC, 1 esophageal) showed any-grade/grade≥3 TEAEs in 96%/59% and treatment-related any-grade/grade≥3 TEAEs in 85%/44%, with common TEAEs (>30%) including alopecia, decreased appetite, fatigue, and nausea (consistent with an MMAE/vedotin ADC profile).