Ivonescimab tops Keytruda in overall survival for first time in lung cancer trial

Akeso and Summit Therapeutics ↗ 5.72% announced on September 2 that their bispecific antibody ivonescimab achieved a statistically significant overall survival improvement over Merck's ↗ 0.86% blockbuster Keytruda in a Phase 3 trial treating PD-L1-positive non-small cell lung cancer, marking the first time a drug has bested pembrolizumab on this measure in this patient population.smmttx+1

The results come from the HARMONi-2 trial, a randomized, double-blind study conducted in China that enrolled patients with locally advanced or metastatic NSCLC whose tumors express PD-L1. Overall survival was a secondary endpoint in the study, which had already met its primary endpoint of progression-free survival in 2024, when ivonescimab nearly doubled median PFS to 11.14 months compared to 5.82 months for pembrolizumab, yielding a hazard ratio of 0.51.biospace+2

A Mounting Case Across Multiple Trials

The OS result from HARMONi-2 adds to a growing body of evidence for ivonescimab, a first-in-class PD-1/VEGF bispecific antibody. Akeso secured Chinese marketing authorization for ivonescimab as a monotherapy for PD-L1-positive non-squamous NSCLC in April 2025 based on earlier PFS data from the same study. The drug is also approved in China for EGFR-mutated NSCLC and, in combination with chemotherapy, for squamous NSCLC based on HARMONi-6, which showed a 34% reduction in the risk of death compared to tislelizumab plus chemotherapy at ASCO 2026.pharmaphorum+2

Questions Remain for Western Markets

Despite the accumulating Chinese data, a key uncertainty hangs over ivonescimab's prospects outside China. The international HARMONi-3 trial previously missed a PFS endpoint at an interim analysis, raising concerns about the drug's efficacy in Western populations. Updated data from that trial released in July showed a consistent OS hazard ratio of 0.76 in both Asian and Western patient subgroups, offering some reassurance. Additional PFS and OS data from HARMONi-3 are expected before year-end.smmttx+2

Summit, which licensed international rights to ivonescimab for $5 billion in 2022, submitted a U.S. biologics license application to the FDA in January for the drug in EGFR-mutated NSCLC, with a regulatory decision expected in November. The company is also running its own international trial, HARMONi-7, comparing ivonescimab head-to-head with Keytruda in PD-L1-positive NSCLC patients outside China.pharmaphorum+2