Akeso and Summit Therapeutics’ experimental drug ivonescimab has met its key secondary goal in a late-stage lung cancer study, showing patients lived longer when treated with the therapy compared to Merck’s blockbuster Keytruda.
The HARMONi-2 trial enrolled patients with locally advanced or metastatic non-small cell lung cancer whose tumors expressed the PD-L1 protein. Researchers randomly assigned participants to receive either ivonescimab or Keytruda as a first-line treatment. An independent monitoring committee confirmed the drug demonstrated statistically and clinically meaningful improvement in overall survival, according to a joint announcement from the companies.
Trial Results Build on Earlier Data
Ivonescimab previously showed promise in the same study at a May 2024 cutoff. Patients receiving the drug reported a median progression-free survival of 11.14 months, compared to 5.82 months for those on Keytruda. The latest analysis confirms the survival benefit extends beyond just delaying tumor growth.
The drug works as a first-in-class bispecific antibody targeting both PD-1 and VEGF, combining immunotherapy with anti-angiogenesis in a single molecule. Akeso and Summit said HARMONi-2 represents the first Phase III randomized controlled trial to demonstrate a significant positive outcome against Keytruda in this patient population.
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Dr. Yu Xia, president and chief executive at Akeso, said in a statement that the company was pleased four Phase III studies of ivonescimab-based regimens had now demonstrated statistically significant benefit in both overall survival and progression-free survival. “These results further reinforce the clinical value of ivonescimab in the treatment of lung cancer,” Xia said. The dual mechanism of action allows the drug to attack cancer cells through multiple pathways simultaneously, potentially reducing the likelihood that tumors develop resistance mechanisms commonly seen with single-target therapies.
Broader Development Program Continues
Beyond the NSCLC findings, the companies are testing ivonescimab across multiple tumor types. A separate Phase III trial called HARMONi-GI1, which enrolled patients with advanced biliary tract cancer, achieved its overall survival goal in August. The drug is also under investigation in the HARMONi-7 study for patients whose tumors show high PD-L1 expression.
Akeso received approval for ivonescimab in non-small cell lung cancer in China last May. The U.S. Food and Drug Administration is currently reviewing the application, with a Prescription Drug User Fee Act decision expected November 14. The FDA’s review encompasses both the clinical efficacy data and safety profile submitted by the companies.
Ivonescimab fits a pattern seen with other bispecific antibodies in oncology, where targeting multiple pathways simultaneously has shown advantages over single-mechanism drugs. The dual approach appears particularly relevant in lung cancer, where tumor environments often develop resistance to monotherapies. By inhibiting VEGF-mediated blood vessel formation alongside PD-1 checkpoint blockade, the drug addresses both tumor growth and immune evasion simultaneously.
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Commercial Outlook and Partnership Structure
Summit secured rights to ivonescimab in the United States, Europe, Canada, Japan, Latin America, the Middle East and Africa through a deal with Akeso valued at up to $5 billion, announced in 2022. The financial commitment reflects expectations the drug could generate significant revenue if approved in major markets.
Analysts at Citi and Evercore ISI estimate the overall survival advantage will likely exceed 30% compared to Keytruda, though the companies have not yet released detailed figures. GlobalData projects ivonescimab will approach mega-blockbuster status by 2032, with annual sales potentially exceeding $9 billion.
Detailed results from the interim overall survival analysis will be presented at an upcoming international medical conference and submitted for publication in a peer-reviewed journal, according to the announcement.
