Dr Ashraf on Ivonescimab vs Pembrolizumab as a First-Line Treatment for PD-L1+ Advanced NSCLC

Noman Ashraf, MD, hematologist-oncologist, Tampa General Hospital, associate professor, medicine, Division of Hematology/Oncology, University of South Florida Health Morsani College discusses the primary findings from the phase 3 HARMONi-2 trial (NCT05899608) evaluating ivonescimab (AK112) vs pembrolizumab (Keytruda) as a first-line treatment for patients with PD-L1–positive, advanced non-small cell lung cancer (NSCLC).

The primary end point of the trial was progression-free survival (PFS), Ashraf explains. Patients treated with ivonescimab achieved a median PFS of 11.14 months (95% CI, 7.33-not evaluable), which was more than double the 5.82-month (95% CI, 5.03-8.21) median PFS observed in the pembrolizumab arm. This PFS improvement translated to a hazard ratio of 0.51 (95% CI, 0.38-0.69; P < .0001), indicating a 49% reduction in the risk of progression with ivonescimab vs pembrolizumab, he states.

Additionally, the objective response rate was higher in the ivonescimab arm, at 50.0% (95% CI, 42.8%-57.2%) compared with 38.5% (95% CI, 31.7%-45.6%) in the pembrolizumab arm, Ashraf continues. Although the overall survival (OS) data remain immature, early results show a promising trend favoring ivonescimab, he adds.

The trial stratified patients by multiple subgroups, including squamous vs nonsquamous histology and different PD-L1 expression levels. Ashraf explained that ivonescimab demonstrated robust and consistent efficacy across all these subgroups, indicating its broad therapeutic potential in patients with NSCLC regardless of histological type or PD-L1 expression. This finding underscores ivonescimab’s versatility in treating diverse presentations of PD-L1–positive, advanced NSCLC.

Notably, patients with brain metastases represented approximately 16% to 19% of the study population. Despite having asymptomatic brain metastases, these patients also derived benefit from ivonescimab treatment. This finding is particularly important, as brain metastases are generally associated with a poor prognosis and represent a challenge in lung cancer management, Ashraf reports. Ashraf highlights that even in this high-risk subgroup, ivonescimab demonstrated efficacy, further supporting its potential as a first-line treatment option for a wide range of patients with PD-L1-positive, advanced NSCLC.

Overall, the HARMONi-2 trial findings indicate that ivonescimab offers improvement in PFS compared with pembrolizumab for PD-L1–positive, advanced NSCLC. Further analysis will be required to assess the agent’s effect on OS, however, early data show that ivonescimab may be a valuable new first-line treatment option in this setting, Ashraf concludes.