Ivo combo beats Tevimbra, but can it beat Keytruda?

Akeso has answered one burning question – whether ivonescimab can beat PD-1 blockade when combined with chemo – with an apparently emphatic yes, courtesy of a "statistically significant and clinically meaningful" PFS win toplined on Tuesday in the first-line lung cancer study Harmoni-6.

Still to be answered, both in chemo-combo and monotherapy settings, is whether a PFS win will translate into an improvement in overall survival. Moreover, Harmoni-6 is a Chinese study that uses Tevimbra as the anti-PD-1 drug whose chemo combo was the comparator; much more relevant for western markets will be a comparison against Keytruda plus chemo.

That's especially relevant for ivonescimab's western partner, Summit Therapeutics, which is running the analogous Harmoni-3 trial; unlike Harmoni-6 this compares ivo plus chemo against Keytruda plus chemo, but isn't due to end until December 2027. Investors see a clearly positive read-across, however, sending Summit shares up 8% on Tuesday, and a further 10% the following morning.

Chemo combo

Akeso's Harmoni-6 combined ivonescimab with chemo in first-line NSCLC patients with squamous histology, and only completed enrolment of 532 subjects in February.

Already at its first interim analysis it has been ruled by the data-monitoring committee to have hit its primary endpoint of PFS versus Tevimbra plus chemo. The trial enrolled patients irrespective of PD-L1 status, and importantly is said to have shown meaningful PFS benefits in PD-L1-positive and negative populations alike.

Full data are being held back for presentation at a scientific meeting, and Evercore ISI's Cory Kasimov wrote in a note to clients that he suspected that Akeso had submitted a placeholder abstract for ASCO. This hasn't been confirmed. however, and the study didn't appear among the ASCO abstract titles that were released on Wednesday.

Ivonescimab's chemo combo win in Harmoni-6 is somewhat analogous to the project's success as monotherapy, in Akeso's Harmoni-2 trial, also in first-line NSCLC but in PD-L1 ≥1% expressers. The latter trial was Chinese, and while the comparator was Keytruda the win was also only on PFS, with OS results representing a crucial catalyst that could come in 2025.

As for the latest success, in Harmoni-6, Akeso has said nothing about any signals in OS, a secondary endpoint. And investors have slightly longer to wait for confirmation of the result in a western study, though it's possible that Summit's Harmoni-3 trial will yield some positive data at interim analyses before the end of 2027.

For now many Summit investors seem comfortable giving ivonesciomab the benefit of any doubt.

Ivonescimab + chemo trials in first-line lung cancer

Source: OncologyPipeline.