Ivonescimab Shows Overall Survival Benefit in Advanced NSCLC
Updated results from the HARMONi-2 trial showed that the investigational bispecific antibody ivonescimab improved overall survival in PD-L1-positive advanced non-small cell lung cancer compared with pembrolizumab, with median survival of 30.8 versus 22.6 months. The benefit was consistent across subgroups, but the trial was conducted entirely in China and used a locally available PD-L1 assay. The control arm of pembrolizumab monotherapy may not reflect global practice, and a global phase III trial is ongoing.
The HARMONi-2 findings, presented at the World Conference on Lung Cancer in Seoul, showed survival curves separating at 12 months and steadily widening in favor of ivonescimab. Subgroup benefits appeared consistent across PD-L1 expression levels, age, and histology, though the invited discussant noted the effect was driven largely by the PD-L1-high group and squamous tumors, which typically carry a worse prognosis.
Ivonescimab also demonstrated an overall survival benefit in the separate global HARMONi trial for EGFR-mutated NSCLC resistant to EGFR inhibitors, which previously showed improved progression-free survival when combined with chemotherapy. A global phase III study, HARMONi-7, is now evaluating ivonescimab specifically in PD-L1-high metastatic disease, and researchers await data on genomic alterations and additional predictive biomarkers.
If confirmed in the ongoing global trial, ivonescimab could offer a chemotherapy-free first-line option for patients with PD-L1-high NSCLC, potentially shifting standard practice away from PD-1 inhibitors. However, the China-only data, use of a locally available assay, and increased toxicity compared with pembrolizumab mean clinicians may remain cautious until broader evidence emerges. Patients could ultimately gain a new treatment choice, but adoption may depend on how results translate across diverse global populations and practice patterns.