Novel antibody-Drug Conjugate sigvotatug Vedotin Shows Promise in Non-Small Cell Lung Cancer Treatment
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A new targeted therapy, sigvotatug vedotin, is demonstrating encouraging results in the fight against non-small cell lung cancer (NSCLC), especially in patients who haven’t previously received taxane chemotherapy. Early clinical data suggests the drug, designed to target integrin beta-6 (IB6), could offer a notable advancement in treatment options.
Anti-Cancer Activity
Sigvotatug vedotin, formerly known as SGN-B6A, is an antibody-drug conjugate (ADC) that works by delivering a potent chemotherapy agent directly to cancer cells. Preclinical studies, as presented by a medical director at the Earle A. Chiles Research institute at Providence Cancer Institute, revealed that inhibiting IB6 enhances the infiltration of tumor-infiltrating lymphocytes, specifically CD8-positive T cells, when used in combination with PD-1 blockade. These findings suggest a synergistic effect, boosting the body’s own immune response against the tumor. Further in vivo models indicated the drug exhibited antitumor activity against a range of cancers, including NSCLC, pancreatic, pharyngeal, and bladder cancers.
Phase 1 Trial Results Demonstrate encouraging Response Rates
The initial findings come from the ongoing phase 1 SGNB6A-001 trial (NCT04389632), a dose escalation and expansion study evaluating single-agent sigvotatug vedotin. Among all 116 patients with NSCLC enrolled in the trial, the confirmed overall response rate (ORR) reached 19.0% (95% CI, 12.3%-27.3%), with 3 complete responses (CRs) and 19 partial responses (PRs).
However, the most compelling results emerged from a subset of patients with nonsquamous NSCLC who were taxane naive – meaning they had not yet received taxane-based chemotherapy. In this group of 42 patients, the ORR climbed to 31.0% (95% CI, 17.6%-47.1%), with 2 CRs and 11 PRs. Notably, these patients also experienced a median progression-free survival (PFS) of 6.4 months (95% CI, 4.5-10.5).
Safety Profile Aligned with Chemotherapy Payload
Treatment-related adverse effects (AEs) observed in the phase 1 trial were generally consistent with the known toxicity profile of the drug’s payload, monomethyl auristatin E. The most frequently reported grade 3 or higher AEs included dyspnea, fatigue, and neutropenia. Pneumonitis was observed in 3 patients, but did not reach grade 3 or higher severity.
Combination Therapy Shows Promise in Advanced NSCLC
More recent data, presented at the 2025 ASCO Annual Meeting, revealed even more promising results.In 21 patients with previously untreated, advanced NSCLC, combining frontline sigvotatug vedotin with pembrolizumab (Keytruda) resulted in a confirmed ORR of 42.9% (95% CI, 21.8%-66.0%). Researchers are continuing to explore this combination in additional patient cohorts within the ongoing phase 1 trial.
phase 3 Trial Underway to Confirm Clinical Benefit
Building on these encouraging findings, the randomized phase 3 Be6A Lung-01 trial (NCT06012435) is now underway. This trial will compare sigvotatug vedotin to docetaxel in patients with previously treated NSCLC, aiming to confirm the clinical benefit observed in earlier studies and further characterize the safety and efficacy of IB6-directed therapy. The ultimate goal is to establish sigvotatug vedotin as a valuable new treatment option for patients battling this challenging disease.
