Akeso and Summit Therapeutics’ giant-killing, PD-1xVEGF bispecific antibody ivonescimab has posted another phase 3 trial win in lung cancer, this time as part of a chemotherapy combination.
An independent data monitoring committee has determined that the HARMONi-6 trial for the first-line treatment of advanced squamous non-small cell lung cancer (NSCLC) has met its primary endpoint of progression-free survival (PFS), Akeso said Tuesday.
At the first pre-specified interim analysis of the 532-patient Chinese study, ivonescimab plus chemotherapy “decisively beat” BeiGene’s PD-1 inhibitor Tevimbra plus chemotherapy, Akeso said. The results—which will be presented at a medical conference later this year—were “statistically significant and clinically meaningful,” the Chinese company added.
Ivonescimab plus chemo excelled in both PD-L1-positive and PD-L1-negative patients and showed a favorable safety profile, with no new signals identified, according to Akeso. The incidence of treatment-related serious adverse events and bleeding events of grade 3 or higher were comparable in both of the study arms.
“This breakthrough not only advances the treatment of non-small cell lung cancer but also marks a significant milestone in global oncology immunotherapy,” Lu Shun, the principal investigator of HARMONi-6, said in a release. “With its combined immune and antiangiogenic mechanisms, ivonescimab offers a promising new treatment option for patients with advanced squamous carcinoma.”
This is the third successful trial of ivonescimab in lung cancer and its second against a PD-1 treatment in NSCLC. In the HARMONi-2 study conducted in China, ivonescimab trounced Merck’s Keytruda as a monotherapy, slashing the risk of disease progression or death in the dual endpoint trial by 49%.
With the HARMONi-6 result, shares of Summit were up 18% on Wednesday. The Florida drugmaker has rights to ivonescimab in the U.S., Europe and Japan, while Akeso controls them in Australia and in China, where it was approved 10 months ago.
Citi analyst Yigal Nochomovitz, Ph.D., said that the success of HARMONi-6 “puts to rest the concern that HARMONi-2 was somehow a ‘fluke,’ and proves the point, with an even higher bar, given the chemo backbone on both arms.” It shows that HARMONi-2 was “anything but a 'one hit wonder.'”
“HARMONi-6 addresses the debate that ivonescimab’s clinical effect over a competing PD-1 will be blunted by chemo,” Nochomovitz wrote in a Tuesday note to investors.
He added that the most recent trial success also has positive implications for Summit’s HARMONi-3 study outside of China, in which ivonescimab plus chemo faces off against Keytruda plus chemo.
While the many PD-1 inhibitors are largely viewed as more similar than different, ivonescimab still needs to beat Keytruda—rather than Tevimbra—in a global population to make a convincing case in the U.S. market.