Akeso says ivonescimab delivers OS win in lung cancer trial

Akeso said Tuesday that its lung cancer drug ivonescimab has, for the first time, clearly extended overall survival (OS) in a pivotal study. In its half-year report, the Chinese biotech disclosed that the final analysis of the Phase III HARMONi-A trial met its OS goal, showing that ivonescimab — partnered with Summit Therapeutics — delivered "a statistically significant and clinically meaningful OS benefit."

The China-only study tested the bispecific PD-1/VEGF antibody in combination with chemotherapy for patients with EGFR-mutated, locally advanced or metastatic non-squamous non–small-cell lung cancer (NSCLC) who had progressed after tyrosine kinase inhibitor therapy.

Results from HARMONi-A, which underpinned Chinese approval of the drug last year for second-line EGFR-mutated NSCLC, showed that when added to chemotherapy, ivonescimab was associated with a 54% progression-free survival (PFS) benefit compared to placebo plus chemotherapy. Median PFS was 7.1 months for the combination arm versus 4.8 months for chemotherapy alone.

However, survival had remained an open question. Earlier interim analyses of HARMONi-A hinted at a diminishing OS benefit, with hazard ratios moving from a 28% death-risk reduction after 10.2 months of median follow-up, to 20% after close to 18 months of follow-up.

'Positive surprise'

The new readout may address a key uncertainty for a drug candidate that previously delivered strong results in tumour progression, but inconsistent survival signals in other trials as well. The OS update "came as a positive surprise," Bernstein analysts noted, with the question of whether ivonescimab extends survival being "the centre of debate…since last year."

In April, ivonescimab won a second nod in China, this time as a first-line therapy for PD-L1-positive NSCLC in patients without EGFR or ALK mutations. That decision was based on results from the Phase III HARMONi-2 study, where ivonescimab met the primary endpoint by achieving an 11.14-month median PFS, a statistically significant improvement when compared to Merck & Co.'s Keytruda (pembrolizumab). However, an interim OS analysis failed to reach statistical significance, despite showing a roughly 22% reduction in the risk of death against Keytruda.

Global data have also been mixed. The Phase III HARMONi trial, which included patients outside China and was reported by Summit at the end of May, showed that ivonescimab plus chemotherapy had a 48% PFS benefit over chemotherapy alone, but missed statistical significance for OS at an interim analysis despite a positive trend. Summit has suggested that additional follow-up could shift the outcome, noting that "median follow-up time for Western patients was less than the median [OS] at the time of the analysis, and these patients may continue to be followed for long-term outcomes."

Amid the clinical results, recent reports have suggested that AstraZeneca is in talks with Summit over a potential deal worth as much as $15 billion for rights to ivonescimab, although the company is also said to be in discussions with other interested parties.