Ivonescimab goes post-checkpoint

Akeso and its partner Summit, already running various pivotal trials of their anti-PD-1 x VEGF bispecific ivonescimab, are now taking on NSCLC patients who have failed on a checkpoint inhibitor. Harmoni-8A will be sponsored by Akeso, so it will be interesting to see if Summit, which has largely echoed its Chinese counterpart, will start a similar US study. Harmoni-8A will pit ivonescimab plus docetaxel against docetaxel alone, chemo still being the standard of care in post-PD-(L)1 patients. This setting has proven tough to crack, with TROP2 now looking like a dead end after the tribulations of AstraZeneca’s Datroway in Tropion-Lung01 and Gilead’s Trodelvy in Evoke-01, despite Gilead once claiming to have found a way forward in a post-checkpoint inhibitor subgroup. Harmoni-8A will add to existing ivonescimab trials in second-line NSCLC following EGFR inhibition. Here Akeso has already reported positive results, from Harmoni-A, while Summit’s Harmoni trial is set to read out mid-year, marking the first global pivotal results for the project. However, the big prize commercially will be first-line NSCLC, where the Chinese Harmoni-2 trial is expected to yield survival data in late 2025/early 2026 – a key test following its PFS win.

Pivotal trials of ivonescimab in NSCLC

Note: *Harmoni-3 inclusion criteria as stated on clinicaltrials.gov mandate "TPS with PD-L1 expression prior to randomisation", but Summit states that this is an all-comers study. Source: OncologyPipeline.