Phase 3 study of sigvotatug vedotin (SV) vs docetaxel (DTX) in previously treated nonsquamous non-small cell lung cancer (NSCLC)

SigVie-002

Patient / Population Intervention / Exposure Comparison Outcome

In patients with previously treated nonsquamous non-small cell lung cancer, sigvotatug vedotin did not improve overall survival compared with docetaxel.

N

703patients

Design

Phase 3 randomised trial of sigvotatug vedotin, an integrin beta-6-directed antibody-drug conjugate, vs docetaxel in patients with nonsquamous NSCLC after prior platinum-based chemotherapy, plus a prior PD-(L)1 inhibitor if they had no known actionable genomic alteration or at least one targeted therapy if they had one (NCT06012435).

Endpoint

Overall survival.

ResultMedian OS 11.9 months with sigvotatug vedotin vs 11.5 months with docetaxel (HR 0.929, 95% CI 0.767-1.126; one-sided P = 0.226). Median PFS by BICR 4.7 vs 4.2 months (HR 0.844, 95% CI 0.699-1.019). In the post-hoc second-line subgroup, median OS was 13.6 vs 11.1 months (HR 0.831, 95% CI 0.658-1.049) and median PFS 5.9 vs 4.2 months (HR 0.795, 95% CI 0.634-0.996). In the third-line or later subgroup, median OS was 10.0 vs 11.9 months (HR 1.187, 95% CI 0.850-1.657). Any-grade treatment-related adverse events occurred in 91% vs 87% and grade 3 or higher in 33% vs 36%. Treatment-related adverse events led to discontinuation in 11% vs 9%.

Peters S, Yamamoto N, Junior WNW, et al. Presented at ESMO Congress 2026, abstract LBA68, 25 October. Not yet published.

Discussion & critique

This large randomised phase 3 trial missed its primary endpoint: sigvotatug vedotin did not significantly improve overall survival over docetaxel, and the PFS confidence interval crossed 1. The favourable second-line trends come from a post-hoc subgroup analysis. They are hypothesis-generating only, and the confidence interval for OS in that subgroup also crossed 1. The abstract does not report blinding, follow-up duration, response rates or the number of deaths. It also found no clear relationship between integrin beta-6 expression and efficacy, which leaves no biomarker to select patients. The proposed next step, combinations with pembrolizumab or a PD-1/VEGF bispecific, relies on phase 1 data that this trial did not test.