ESMO: Ivonescimab beats BeOne PD-1 in first-line lung cancer

Akeso and Summit Therapeutics have shared the full data from the HARMONi-6 trial of PD-1xVEGF bispecific ivonescimab as a first-line therapy for squamous non-small cell lung cancer (NSCLC) at ESMO, headlined by a 40% reduction in the risk of disease progression or death.

The result – in a Chinese population – raises further hope that ivonescimab could offer a step up in efficacy over first-line immunotherapy for NSCLC, although ESMO commentator Prof Myung-Ju Ahn of Sungkyunkwan University School of Medicine in South Korea said that changes to clinical practice will depend on showing similar benefits in an ex-China population – currently under test in the Harmoni-3 trial.

She also suggested ivonescimab will need to show an improvement in overall survival (OS) in the study to displace immunotherapy, which is the go-to therapy for NSCLC.

Ivonescimab generated headlines when it bested MSD's best-selling PD-1 inhibitor Keytruda (pembrolizumab) in the HARMONi-2 trial in previously untreated, PD-L1-positive squamous and non-squamous NSCLC, with some describing it as a potential 'Keytruda killer', although expectations were dented after it was unable to demonstrate an improvement in OS in the HARMONi study when used as a second-line or later therapy for EGFR-mutant NSCLC.

In HARMONi-6, ivonescimab plus chemo bested BeOne's PD-1 inhibitor Tevimbra (tislelizumab) plus chemo, with median progression-free survival (PFS) of 11.1 months and 6.9 months, respectively.

That four-month improvement in PFS was accompanied by a 45% improvement in median PFS for patients whose tumours expressed the biomarker PD-L1 at levels below 1%, which Ahn said was "an insightful and important finding" that suggests ivonescimab is working across a broad-range of PD-L1 levels.

There's no word yet on OS as the data remains immature, according to Akeso and Summit, but the companies have indicated they are hopeful of a significant benefit on this outcome as the median duration of response data is strong, at 11.2 months with ivonescimab and 8.4 months with Tevimbra.

Summit also gave an update on the HARMONi-3 trial, which is being run with a similar protocol to HARMONi-6, including patients whose tumours have a broad range of PD-L1 levels, but replaces Tevimbra with Keytruda as the comparator and will include patients with both squamous and non-squamous NSCLC.

The PFS and OS readouts for each histological group will also be split and reported at different times, with Summit anticipating the first squamous data next year and non-squamous results in 2027.