Multinational phase 1 study of sigvotagug vedotin for advanced non-small cell lung cancer: dose expansion results

Integrin beta-6 (IB6) is highly expressed in non-small cell lung cancer (NSCLC) and is potentially associated with poor outcomes. Sigvotagug vedotin (SV) is a novel IB6-directed antibody-drug conjugate with acceptable safety and encouraging antitumor activity in the dose escalation part of the multinational SGNB6A-001 trial. Results for dose-expansion regimen in previously treated advanced NSCLC (aNSCLC; n=117) have now been published. Dose expansion explored three regimens: 1.25 mg/kg total body weight (TBW) on days 1 and 8 of an 21-day cycle; 1.5 mg/kg TBW on days 1 and 15 of a 28-day cycle; and 1.8 mg/kg adjusted ideal body weigt (AiBW) once every 2 weeks. Any-grade and grade ≥ 3 treatment-emergent adverse events were reported by 98% and 48% of patients, respectively. Objective response rate and median duration of response were 19% and 11.3 months in the overall population, respectively, and 29% and 12.8 months in patients with nonsquamous, taxane-naïve NSCLC. Based on pharmacokinetics and clinical data, 1.8 mg/kg AiBW once every 2 weeks is the recommended dose to be further investigated. The authors conclude that SV demonstrated a manageable safety profile and promising antitumor efficacy with durable responsed in aNSCLC.