Ivonescimab monotherapy hinted at better progression-free survival than its rival and has been approved by China’s regulator.
Ivonescimab monotherapy improves progression-free survival in patients with PD-L1–expressing advanced non-small cell lung cancer (aNSCLC) compared with pembrolizumab, new Chinese research suggests.
These findings underpinned regulatory approval by Chinese drug regulator, the National Medical Products Administration, for the first-line treatment of some patients with non-small cell lung cancer.
The HARMONi-2 phase 3 trial randomly assigned treatment-naïve adults with locally advanced or metastatic PD-L1–positive (tumour proportion score [TPS] ≥1%) aNSCLC without EGFR mutations or ALK rearrangements to receive either ivonescimab (20mg/kg) or pembrolizumab (200mg) monotherapy every three weeks.
Ivonescimab is a new bispecific antibody targeting programmed cell death protein 1 and vascular endothelial growth factor.
This study, of 398 adults from 55 centres in China, found that patients taking ivonescimab had a significantly longer median progression-free survival of 11.1 months compared with pembrolizumab at 5·8 months. This equated to a stratified hazard ratio of 0·51.
“The efficacy was consistent in patients with low and intermediate and high PD-L1 expression, and also in patients with squamous and non-squamous non-small cell lung cancer,” the authors wrote in The Lancet.
“Immune-related adverse events of grade 3 or higher were similar between the ivonescimab and pembrolizumab groups.”
These events occurred in 29% of the ivonescimab group compared to 16% of the pembrolizumab group overall, and rates were comparable across treatments even in patients with squamous cell carcinoma.
“Ivonescimab significantly improved progression-free survival with a manageable safety profile as first-line treatment in patients with locally advanced or metastatic PD-L1-positive non-small cell lung cancer, and could provide a novel treatment option for those patients, regardless of non-small cell lung cancer histology,” the authors wrote.
Associate Professor Steven Kao, medical oncologist at Chris O’Brien Lifehouse, praised the “well-conducted” study.
“The results are really quite amazing,” he said.
“The performance of the control arm [pembrolizumab] was pretty reasonable. And that makes it even more remarkable that ivonescimab seems to be so much better, with that impressive hazard ratio of 0.51.”
Nevertheless, the study’s Chinese population would limit its generalisability to Australia, and the trial didn’t compare the standard of care for PD-L1 lows – pembrolizumab plus chemotherapy – to this new drug, he said.
“The subgroup [results] for PD-L1 high and PD-L1 low both looked pretty impressive compared to pembrolizumab, but the clinical question, ‘Would ivonescimab be better than chemo plus pembro?’ is unanswered at the moment,” he said.
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The lack of excess bleeding risk in these squamous cell cancer patients was another interesting finding, Professor Kao said.
The study found that patients with squamous non-small cell lung cancer had significantly better progression-free survival on the new medication, at a median of 9.7 months and a hazard ratio of 0.50. These patients account for at least one in four non-small cell lung cancer cases.
Anti-VEGF monoclonal antibodies such as bevacizumab are contraindicated in patients with squamous non-small cell lung cancer because of their significantly higher risk of bleeding or massive haemoptysis leading to death, Professor Kao said.
The study’s finding, that there was no evidence of bleeding complications or prohibitive toxicity in these patients, was “reassuring”, he said.
“I think it’s an impressive study. [But] I would like to see this in a more global setting before I would say that it is practice changing,” he said.
