Sigvotatug vedotin (IB6 ADC) + pembrolizumab hits 57% ORR in PD-L1⁺ NSCLC

Sigvotatug vedotin, an integrin β6–directed vedotin ADC, was paired with pembrolizumab in the Phase 1 SGNB6A-001 escalation/expansion trial (NCT04389632). Thirty-one patients with advanced NSCLC (n = 19) or HNSCC (n = 11) received SV 1.8 mg/kg Q2W plus pembro 400 mg Q6W. The combination was well-tolerated with 6% of patients discontinuing treatment due to TRAEs (all renal events). Any-grade and ≥G3 TEAEs were 87% and 35%, with pneumonitis occurring in 10% of patients (all ≤G2). Among efficacy-evaluable cases, ORR reached 57% (4/7; confirmed 29%) in PD-L1 TPS≥1 NSCLC (58% of NSCLC patients in the study) and 38% (3/8) in first-line HNSCC. These results exceed the pembrolizumab monotherapy ORR benchmarks of ~45% (PD-L1-high NSCLC, KEYNOTE-024) and 19% (CPS≥1 HNSCC, KEYNOTE-048).