Ivonescimab significantly improved OS vs pembrolizumab at a prespecified interim analysis of the HARMONi-2 trial in first-line PD-L1–positive NSCLC.
Ivonescimab (SMT112; AK112) produced a statistically significant and clinically meaningful improvement in overall survival (OS) vs pembrolizumab (Keytruda), as assessed by an independent data monitoring committee, in patients with first-line PD-L1-positive non–small cell lung cancer (NSCLC) at a prespecified interim analysis of the phase 3 HARMONi-2 trial (NCT05499390).¹
HARMONi-2 is a randomized, double-blind, multicenter, registrational trial evaluating ivonescimab, a PD-1/VEGF bispecific antibody, vs pembrolizumab as first-line treatment for patients with locally advanced or metastatic NSCLC whose tumors express PD-L1 (tumor proportion score [TPS] ≥ 1%). The trial previously met its primary end point of progression-free survival (PFS) at an earlier interim analysis. Detailed OS data will be presented at a future international medical meeting and published in a peer-reviewed journal.
“We are pleased that the fourth phase 3 study of an ivonescimab-based regimen has now demonstrated statistically significant benefit in both OS and PFS,” Yu Xia, PhD, founder, chairwoman, president, and chief executive officer of Akeso, stated in a news release. “These results further reinforce the clinical value of ivonescimab in the [management] of lung cancer. We thank the investigators, clinical teams and patients who participated in the HARMONi-2 study for their important contributions. To date, ivonescimab has [generated] dual positive OS and PFS outcomes across multiple phase 3 head-to-head trials vs PD-1/PD-L1[–directed] therapies. This growing body of evidence strengthens our confidence in its potential across a broader range of solid tumors. With its unique dual mechanism of action combining immunotherapy and anti-angiogenesis, we believe ivonescimab offers a more effective treatment option for patients.”
Ivonescimab vs Pembrolizumab in First-Line PD-L1+ NSCLC: HARMONi-2 Highlights
Notably,
HARMONi-2 randomly assigned 398 patients across 55 centers in China 1:1 to receive ivonescimab at 20 mg/kg or pembrolizumab at 200 mg every 3 weeks.3 Eligible patients had untreated locally advanced or metastatic NSCLC, an ECOG performance status of 0 or 1, and PD-L1–positive tumors (TPS ≥ 1%); randomization was stratified by histology, clinical stage, and PD-L1 expression level. PFS by blinded independent radiographic review committee served as the primary end point. OS is a key secondary end point.1
At the preplanned interim analysis, the median PFS was 11.14 months with ivonescimab vs 5.82 months with pembrolizumab, corresponding to a 49% reduction in the risk of disease progression or death (HR, 0.51).1,2 Additionally, an interim OS analysis conducted when the data were 39% mature showed a clinically meaningful OS improvement with ivonescimab vs pembrolizumab (HR, 0.777), translating to a 22.3% reduction in the risk of death.2
The HARMONi-2 trial OS readout adds to a series of positive phase 3 results for ivonescimab. In August 2026,
