Dr Sanborn on Early Efficacy and Security Knowledge 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 on the Earle A. Chiles Research Institute at Providence Cancer Institute, shared preclinical and early medical information with the novel integrin beta-6 (IB6)–directed antibody-drug conjugate (ADC) sigvotatug vedotin (previously SGN-B6A) for sufferers with non–small cell lung most cancers (NSCLC).

Preclinical research demonstrated that inhibition of IB6 enhanced tumor-infiltrating lymphocyte infiltration, together with CD8-positive T cells, when mixed with PD-1 blockade, Sanborn started. In vivo fashions additionally confirmed sigvotatug vedotin had antitumor exercise throughout a number of tumor varieties, together with NSCLC, pancreatic, pharyngeal, and bladder cancers, she reported.

Additionally, within the first-in-human, part 1 SGNB6A-001 trial (NCT04389632), single-agent sigvotatug vedotin was evaluated throughout a number of dosing regimens, Sanborn continued. Among sufferers with NSCLC (n = 116), the ADC demonstrated a confirmed general response charge (ORR) of 19.0% (95% CI, 12.3%-27.3%), together with 3 full responses (CRs) and 19 partial responses (PRs). In a subset of sufferers 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 opposed results (AEs) noticed with sigvotatug vedotin on this examine had been typically per the recognized chemotherapy-related toxicity of its monomethyl auristatin E payload, Sanborn acknowledged. The commonest grade 3 or greater AEs included dyspnea, fatigue, and neutropenia. Pneumonitis occurred in 3 sufferers however was not grade 3 or greater in severity.

At the 2025 ASCO Annual Meeting, up to date findings confirmed that in sufferers with untreated, superior NSCLC (n = 21), frontline sigvotatug vedotin mixed with pembrolizumab (Keytruda) led to a confirmed ORR of 42.9% (95% CI, 21.8%-66.0%), Sanborn added. This mixture is being additional explored in further cohorts of the continuing part 1 trial, she famous.

Based on these findings, the randomized part 3 Be6A Lung-01 trial (NCT06012435) is now evaluating sigvotatug vedotin vs docetaxel in beforehand handled NSCLC, with the purpose of confirming medical profit in a bigger inhabitants and additional characterizing security and efficacy of IB6-directed remedy, Sanborn concluded.