Ivonescimab cuts death risk 27% versus Keytruda in Phase III NSCLC trial

Updated overall survival data from the Phase III HARMONi-2 trial show that ivonescimab monotherapy reduced the risk of death by 27% compared with Merck's Keytruda (pembrolizumab) monotherapy in patients with PD-L1-positive advanced non-small cell lung cancer (NSCLC), according to data presented at the IASLC 2026 World Conference on Lung Cancer. The result extends ivonescimab's earlier progression-free survival (PFS) win in the same study into an overall survival (OS) benefit.

In the protocol-specified interim OS analysis of 398 patients at a median follow-up of 36.0 months, median OS was 30.8 months in the ivonescimab arm versus 22.6 months for pembrolizumab — an 8.2-month difference — with a stratified hazard ratio (HR) of 0.73 (95% CI: 0.57, 0.95; p=0.009). The PD-L1 high subgroup (PD-L1 score ≥50%, n=168) showed a more pronounced effect, with a descriptive HR of 0.58 (95% CI: 0.38, 0.89), though this subgroup analysis was not formally powered. Serious treatment-related adverse events occurred in 29.9% of patients on ivonescimab versus 21.6% on pembrolizumab; discontinuation rates were similar at 4.1% versus 5.0%, respectively, with no new safety signals identified at the longer follow-up.

Ivonescimab is a tetravalent bispecific antibody that simultaneously blocks PD-1 and VEGF within a single molecule, with cooperative binding designed to preferentially concentrate activity in the tumor microenvironment where both targets are more highly expressed. Akeso, Inc. (HKEX: 9926.HK) engineered the molecule and holds China rights; Miami-based Summit Therapeutics Inc. (Nasdaq: SMMT) holds rights in North America, Europe, and other territories outside China.

The HARMONi-2 study was conducted in China, and Akeso received NMPA marketing authorization based on its primary PFS analysis — which had demonstrated an HR of 0.51 (95% CI: 0.38, 0.69; p<0.0001) — in April 2025. The OS data now reported represent the trial's key secondary endpoint. The study is single-region, and its results are not directly transferable to regulatory submissions in Summit's territories; ivonescimab remains investigational in the US and EU.

The OS result is nonetheless consequential for Summit's global program. HARMONi-7 is a randomized, double-blind Phase III study comparing ivonescimab monotherapy with pembrolizumab in first-line metastatic NSCLC with high PD-L1 expression. The trial is designed to assess both PFS and OS, and the stronger OS signal observed in the PD-L1 ≥50% subgroup of HARMONi-2 (HR 0.58) provides additional support for the strategy being tested globally, although the subgroup analysis itself was descriptive and not formally powered.

Pembrolizumab remains a benchmark first-line therapy in PD-L1-positive NSCLC, making a head-to-head OS advantage in HARMONi-2 clinically significant despite the study being conducted exclusively in China. The result adds to a growing body of positive Phase III evidence for ivonescimab across NSCLC settings, including OS-positive HARMONi-A and HARMONi-6 studies and the global HARMONi trial in EGFR-mutant disease. HARMONi-6 supported an August 2026 NMPA approval for first-line squamous NSCLC, while Summit's BLA for ivonescimab plus chemotherapy in EGFR-mutant NSCLC after TKI failure is under US FDA review with a November 14, 2026 PDUFA date.

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