Ivonescimab Beats Keytruda on Overall Survival in HARMONi-2

Akeso, Summit Therapeutics’ China partner, said the Phase 3 HARMONi-2 trial met its key secondary endpoint of overall survival at a pre-specified interim analysis, giving ivonescimab a statistically significant and clinically meaningful survival advantage over Merck’s Keytruda in first-line PD-L1-positive non-small cell lung cancer. Summit (SMMT) shares closed at $14.60 on Wednesday and jumped about 14% to roughly $16.60 in Thursday trading.

The result matters because Keytruda is the standard of care and the top-selling drug in oncology. HARMONi-2 is a randomized, double-blind, registrational trial run in China that put ivonescimab head-to-head against pembrolizumab in patients whose tumors express PD-L1. It already met its primary endpoint of progression-free survival in May 2024, with a median of 11.14 months versus 5.82 months for pembrolizumab, making it the first randomized, double-blind Phase 3 trial to show a positive outcome against Keytruda in this setting. The new readout adds the survival endpoint on top of that progression-free benefit.

Ivonescimab is a PD-1/VEGF bispecific antibody that blocks the PD-1 immune checkpoint and traps VEGF, the protein that feeds tumor blood vessels, in a single molecule. It is already approved in China for this indication and two others. Akeso did not release the detailed OS numbers, saying it will present them at an upcoming medical meeting and publish them in a peer-reviewed journal.

For Summit, which holds ex-China rights to the drug, the caveat is familiar: HARMONi-2 is a China-only trial, and the FDA wants Western data before a clean review. Summit is running the global Phase 3 HARMONi-3 trial to confirm the benefit, and its nearest real catalyst remains the November 14 PDUFA date for ivonescimab in EGFR-mutant NSCLC.

The readout extends a long streak for the molecule. Ivonescimab has now logged five positive Phase 3 readouts, including the HARMONi-GI1 biliary tract cancer win in August, and Akeso’s chief executive said this is the fourth ivonescimab-based regimen to show a statistically significant benefit on both overall survival and progression-free survival.

What to watch next: the detailed HARMONi-2 OS data at the next medical conference, the HARMONi-3 global readout, and the November 14 PDUFA decision.

Source: Akeso press release