Akeso and Summit Therapeutics’ experimental dual-acting cancer drug helped people with lung cancer live about eight months longer than those who got Merck & Co.’s Keytruda in a Phase 3 clinical trial, and showed an even stronger benefit in people whose tumors express high levels of a protein that both medicines target.
The findings could help Akeso and Summit shed doubts about the promise of their drug, called ivonescimab, as well as other experimental therapies that target the proteins “PD-1” and “VEGF” as potential heirs to Keytruda as a backbone of lung cancer care.
Data from “HARMONi-2” have been among the most closely watched in cancer research over the last two years, as the study was the first late-stage trial to show that ivonescimab might be better than Keytruda in helping to significantly delay disease progression or death. The latest data cut, evaluating overall survival, also demonstrated a benefit.
Wall Street analysts have raised concerns about the ivonescimab data, questioning whether the China-based trials run by Akeso — its original developer — can translate into a broader global population because of differences in patient characteristics and treatment practices.
The latest findings, released at the World Conference on Lung Cancer meeting in South Korea, could put at least some of those to rest. In the trial population broadly, the relative risk of death when taking ivonescimab was 27% lower than when taking Keytruda. Those who got ivonescimab lived a median 30.8 months, compared with 22.6 months for those who got the Merck immunotherapy.
Results from a smaller group of patients also raised some hopes that ivonescimab will succeed in one of the big Phase 3 trials it will use to support approval in the U.S. and elsewhere. It has already gained approval in China.
That trial, titled HARMONi-7, is focused on the group of non-small cell lung cancer patients whose disease expresses high levels of PD-L1, the protein Keytruda latches onto and one of the two ivonescimab does. In that group of patients, the relative risk of death was reduced by 42% among those who got ivonescimab. Importantly, that group of patients is the only one in lung cancer for which Keytruda is typically used as a single agent.
Analysts like TD Cowen’s Tyler Van Buren scored the results as a clear win, writing in a client note that they “not only validate ivonescimab's earlier [progression free survival] benefit, but also strengthen confidence that a PD-1/VEGF bispecific can outperform PD-1 monotherapy on the endpoint that matters most to physicians.”
Meanwhile, Leerink Partners analyst Daina Graybosch remains skeptical. In her own note, she pointed to overall survival numbers in the wider population that fell short of what “Sac-TMT” — an antibody drug conjugate developed by Merck and a Chinese biotechnology company named Kelun — showed in a similar population. That drug reduced the relative risk of death by 45%.
Thus, the HARMONI-2 data adds “uncertainty on whether ‘bio-better VEGF/PD-1’ or ‘bio-better chemo’ is more likely to inherit [Keytruda] revenues,” Graybosch wrote.
