Just one week after Summit Therapeutics and Akeso’s bispecific antibody ivonescimab passed muster with Chinese regulators, the drug has pulled off another feat by staring down the PD-1 king Keytruda in non-small cell lung cancer (NSCLC).
In the phase 3 HARMONi-2 trial, solo ivonescimab delivered a statistically significant and clinically meaningful improvement in progression-free survival (PFS) over Keytruda monotherapy, in turn meeting its primary endpoint, Summit said late this week.
The study, carried out only in China by Akeso, pitted the drugs against one another in patients with locally advanced or metastatic NSCLC with PD-L1-expressing tumors.
Whereas Keytruda targets the PD-1 protein to help immune cells kill cancer, ivonescimab binds to both PD-1 and the vascular endothelial growth factor (VEGF) protein. Summit says this dual mechanism could help separate its drug from the pack in solid tumors, given that there is potentially higher expression of both PD-1 and VEGF in tumor tissue—and the tumor microenvironment—versus normal tissue in the body.
Ivonescimab’s benefit in PFS—which describes the length of time during and after treatment that a patient lives without their disease getting worse—was shown across multiple subgroups, including those with PD-L1 low expression, PD-L1 high expression, and those with squamous and non-squamous histologies, Summit explained.
While Summit and Akeso’s results are promising, the partners still have their work cut out if they hope to go up against Keytruda and other approved PD-1 drugs in the United States. For one, ivonescimab would likely need to prove its overall survival (OS) benefit—and not just PFS—to gain a monotherapy approval in NSCLC. Further, the China-only trial design could make it challenging to secure an FDA green light, if the agency's precedent holds.
Summit and Akeso did not lay out detailed results. The partners say they plan to present their findings from the head-to-head trial at a major medical conference later this year.
Still, Evercore ISI analyst Cory Kasimov called the head-to-head results “very encouraging,” noting that Summit and Akeso’s trial win is reportedly the first time a phase 3 candidate has demonstrated a statistically significant PFS improvement versus Keytruda in NSCLC.
Other analysts were impressed, too, such as Citigroup’s Yigal Nochomovitz, who said the results signify the “high potential of ivonescimab not only in lung but across multiple solid tumors,” according to Bloomberg.
Miami-based Summit holds the license to ivonescimab in the U.S., Canada, Europe and Japan, while Akeso is in control of the drug in China and Australia, according to Summit’s press release.
Summit’s stock skyrocketed roughly 270% Thursday on news of the trial results, though shares were down about 21% on Friday morning.
Summit and Akeso’s Keytruda-topping results come about a week after ivonescimab snagged an approval in China in combination with chemotherapy to treat EGFR-mutated locally advanced or metastatic non-squamous NSCLC in patients whose disease progressed after therapy with tyrosine kinase inhibitors (TKIs).
Aside from the Keytruda monotherapy trial, Akeso and Summit are also testing ivonescimab in several other head-to-head settings, including as a combination with chemotherapy against BeiGene’s Tevimbra in locally advanced or metastatic squamous NSCLC, and against Keytruda again as a potential first-line treatment in squamous NSCLC patients.