The interim analysis published online on 31 May 2026 in The Lancet reviewed data from 532 randomized patients, 266 per group.
Study Design
From August 2023 to January 2025, 761 patients were screened at 50 hospitals in China, with 532 randomized and assigned in 1:1 ratio to either ivonescimab or tislelizumab, each combined with paclitaxel and carboplatin over four cycles. This was followed by maintenance therapy with the assigned drug as monotherapy. Median age was 64 years, 93 percent were male. Participants had to be age 18-75 with ECOG performance status 0 or 1 and inoperable stage IIIB, IIIC or IV tumors. The primary endpoint of the double-blind study was progression-free survival as assessed by an independent radiology committee, with overall survival as an important secondary endpoint.
Why the Interim Analysis Was Accelerated
Overall survival analysis was originally planned after approximately 225 deaths, but was triggered after 204 events to meet regulatory timelines. As of the data cutoff 27 February 2026, 84 of 266 ivonescimab-treated patients had died (32 percent) versus 120 of 266 in the tislelizumab group (45 percent). At 12 months, 78.9 percent of the ivonescimab group survived compared to 72.2 percent of the control group. At 24 months, survival was 64.7 percent versus 48.6 percent.
Comparison: Where Earlier Drugs Reached Their Limits
Earlier VEGF drugs could slow tumor growth but struggled to actually extend patient survival. Ivonescimab, by contrast, is a bispecific antibody targeting both PD-1 and VEGF. Within the study itself, results differed by tumor PD-L1 status under tislelizumab plus chemotherapy. Tislelizumab patients with PD-L1 value of at least 1 percent survived a median 27 months, while those below 1 percent survived about 19 months. Under ivonescimab plus chemotherapy, so many participants in both PD-L1 groups remained alive at evaluation that a median overall survival could not be calculated. For context, these results come from China, while the global study HARMONi-3 was recruiting in more than 15 countries including the US as of 1 June 2026 to test effectiveness in other populations.
Safety Profiles Differed
Grade 3 or higher adverse events occurred in 69.2 percent under ivonescimab versus 58.9 percent under tislelizumab. Bleeding of any grade occurred twice as often under ivonescimab as under tislelizumab. Squamous lung tumors often lie near large lung blood vessels, and VEGF blockade can prevent their repair, potentially causing fatal bleeding. Shun Lu and his team called ivonescimab plus chemotherapy's safety profile manageable and consistent with previous reports, with no new safety signals. Sivraj Muralikrishnan found the safety data reassuring, noting that grade 3 severe bleeding occurred in 2.6 percent under ivonescimab versus 0.8 percent in the comparison arm. He assessed the increase in grade 3 adverse events as relatively small given the magnitude of benefit.
Approval in China, Global Review Ongoing
On 12 August 2026, Akeso announced that China's drug authority NMPA approved supplementary authorization of ivonescimab plus chemotherapy as first-line treatment for advanced squamous lung cancer. In the US, ivonescimab was not yet approved as of 1 June 2026.
Suresh Ramalingam, executive director of Winship Cancer Institute at Emory University, called the survival benefit encouraging but noted the study ran only in China, and transferability to other populations requires further study. Oncologist Deborah Doroshow pointed out that the immunotherapy-treated control group lived an average six months longer than expected, raising questions about study population representativeness. ASCO discussant Julie Brahmer stressed the results showed efficacy only for Chinese patients and noted exclusion of patients over 75 years. ASCO lung cancer expert David R. Spigel called the study the first major prospective examination showing superiority of this bispecific therapy plus chemotherapy over the established standard of PD-1 inhibitor plus chemotherapy in advanced squamous lung cancer, but also noted pending global efficacy data. The study was funded by Akeso Biopharma. Sponsors participated in data collection, analysis and interpretation.
Global Trial: Recruitment in 15+ Countries as of June 2026
The global study HARMONi-3 was recruiting in more than 15 countries, including the US, as of 1 June 2026 to test ivonescimab in metastatic non-small-cell lung cancer with both squamous and non-squamous histology. Summit Therapeutics, the licensee, planned to present progression-free survival results in squamous patients in the second half of 2026, with results in non-squamous patients expected in the first half of the following year.