Dr Sanborn on Early Efficacy and Safety Data With Sigvotatug Vedotin Plus Pembrolizumab in NSCLC

"[There was also] a phase 1 dose escalation and expansion study of single-agent sigvotatug vedotin, SGNB6A-001 [NCT04389632]. In that study, [among] patients with NSCLC, the confirmed ORR was [19.0%]. However, when looking at the patient population that had nonsquamous NSCLC and who were taxane naive, the ORR was 31.0%."

Rachel E. Sanborn, MD, medical director of the Thoracic Oncology Program and the Phase I Clinical Trials Program at the Earle A. Chiles Research Institute at Providence Cancer Institute, shared preclinical and early clinical data with the novel integrin beta-6 (IB6)–directed antibody-drug conjugate (ADC) sigvotatug vedotin (formerly SGN-B6A) for patients with non–small cell lung cancer (NSCLC).

Preclinical studies demonstrated that inhibition of IB6 enhanced tumor-infiltrating lymphocyte infiltration, including CD8-positive T cells, when combined with PD-1 blockade, Sanborn began. In vivo models also showed sigvotatug vedotin had antitumor activity across multiple tumor types, including NSCLC, pancreatic, pharyngeal, and bladder cancers, she reported.

Additionally, in the first-in-human, phase 1 SGNB6A-001 trial (NCT04389632), single-agent sigvotatug vedotin was evaluated across multiple dosing regimens, Sanborn continued. Among patients with NSCLC (n = 116), the ADC demonstrated a confirmed overall response rate (ORR) of 19.0% (95% CI, 12.3%-27.3%), including 3 complete responses (CRs) and 19 partial responses (PRs). In a subset of patients with nonsquamous, taxane-naive NSCLC (n = 42), the confirmed ORR was 31.0% (95% CI, 17.6%-47.1%), with 2 CRs and 11 PRs, and a median progression-free survival (PFS) of 6.4 months (95% CI, 4.5-10.5).

Treatment-related adverse effects (AEs) observed with sigvotatug vedotin in this study were generally consistent with the known chemotherapy-related toxicity of its monomethyl auristatin E payload, Sanborn stated. The most common grade 3 or higher AEs included dyspnea, fatigue, and neutropenia. Pneumonitis occurred in 3 patients but was not grade 3 or higher in severity.

At the 2025 ASCO Annual Meeting, updated findings showed that in patients with untreated, advanced NSCLC (n = 21), frontline sigvotatug vedotin combined with pembrolizumab (Keytruda) led to a confirmed ORR of 42.9% (95% CI, 21.8%-66.0%), Sanborn added. This combination is being further explored in additional cohorts of the ongoing phase 1 trial, she noted.

Based on these findings, the randomized phase 3 Be6A Lung-01 trial (NCT06012435) is now evaluating sigvotatug vedotin vs docetaxel in previously treated NSCLC, with the goal of confirming clinical benefit in a larger population and further characterizing safety and efficacy of IB6-directed therapy, Sanborn concluded.