Patients with newly diagnosed advanced lung cancer who received the experimental antibody ivonescimab lived a median of 30.8 months, compared with 22.6 months for those given Keytruda. The figures come from overall survival results from the HARMONi-2 trial, which drugmaker Akeso announced on Sept. 15 following their presentation at the World Conference on Lung Cancer in Seoul. Ivonescimab lowered the risk of death by 27%.
Two limits belong at the top. HARMONi-2 was a single-region study conducted in China, with all data generated, managed, and analyzed by Akeso, according to its U.S. partner, Summit Therapeutics. Ivonescimab is approved in China but not by the FDA or European regulators, so the result does not change what U.S. oncologists can prescribe today.
The finding still carries weight for American patients. Keytruda is a widely used first-line immunotherapy for lung cancer, and Akeso says HARMONi-2 is the first randomized, double-blind phase 3 trial to show statistically significant survival and progression benefits over it.
A Survival Gap That Widened Over Three Years
HARMONi-2 enrolled 398 patients with advanced non-small cell lung cancer whose tumors tested positive for PD-L1, a protein that helps predict how well immunotherapy may work. Each patient received one drug alone: 198 got ivonescimab, and 200 got Keytruda (pembrolizumab).
As of an Aug. 20, 2026, data cutoff, median follow-up reached 36 months, and 234 patients had died. At two years, 57.9% of ivonescimab patients were alive, compared with 48.0% on Keytruda. At three years, the figures were 45.0% and 33.1%.
The benefit looked strongest in patients with high PD-L1 levels, where median survival had not yet been reached on ivonescimab, compared with 23.2 months on Keytruda. In patients with lower PD-L1 levels, median survival was 28.5 months versus 22.1 months, but the statistical range for that group crossed the point of no difference. Summit noted that these subgroup comparisons were descriptive and were not formally designed to prove a benefit on their own.
Ivonescimab blocks two targets with one molecule: PD-1, the same immune checkpoint Keytruda targets, and VEGF, a signal tumors use to grow blood vessels. The trial first showed in 2024 that the drug delayed progression, with median progression-free survival of 11.14 months versus 5.82 months, and China approved it for this use in 2025.
The survival result also strengthened from an earlier look. Fierce Pharma reported that an unplanned interim analysis requested by Chinese regulators had shown a smaller 22.3% reduction in the risk of death. Akeso CEO Michelle Xia told the outlet, "We've become something of a bellwether for the entire PD-1xVEGF space."
Safety Signals and the Single-Country Question
Serious treatment-related side effects occurred in 29.9% of ivonescimab patients and 21.6% of Keytruda patients, although ivonescimab patients stayed on treatment longer, a median of 14 cycles versus 10. Side effects led 4.1% of ivonescimab patients and 5.0% of Keytruda patients to stop treatment. One ivonescimab patient and three Keytruda patients died of treatment-related causes.
Akeso said it saw no apparent increase in bleeding among patients with squamous cell tumors that had features usually considered high risk for VEGF-blocking drugs. That is a company claim that independent reviewers have not yet assessed.
In evidence terms, HARMONi-2 was a randomized, double-blind phase 3 trial, and survival was a secondary goal tested in a protocol-specified interim analysis. The results were released through a conference presentation and company statements, and the study was sponsored by Akeso. After stopping study treatment, fewer ivonescimab patients than Keytruda patients received additional cancer therapy, 36.4% versus 46.0%.
The biggest open question is whether results from Chinese patients apply to U.S. patients. When the trial's earlier data came out in 2024, Fierce Pharma noted that Leerink Partners analysts pointed to wider use of anti-VEGF drugs in Asia and questioned whether doctors' familiarity with that drug class affected how often patients stopped treatment. Summit's separate global HARMONi trial, which tested ivonescimab with chemotherapy in patients with EGFR-mutated lung cancer, has shown a survival trend in Western patients similar to that in Asian patients with longer follow-up, although the Western result on its own was not statistically conclusive.
Summit President and Co-CEO Maky Zanganeh said the updated data "reinforce our confidence in the HARMONi results."
Trials, Testing, and the November FDA Deadline
The people most likely to be affected are those newly diagnosed with advanced non-small cell lung cancer whose tumors express PD-L1. Patients can ask their oncologist for both PD-L1 and genomic test results, since tumors with targetable mutations are often treated differently.
For U.S. patients, the only current route to ivonescimab is a clinical trial, and openings are limited. U.S. sites for HARMONi-3, listed on ClinicalTrials.gov, include Cedars-Sinai Medical Center in Los Angeles and Banner University Medical Center in Phoenix, but those sites currently show as active and not recruiting. HARMONi-3 compares ivonescimab plus chemotherapy with Keytruda plus chemotherapy. Fierce Pharma reported that the study recently missed the statistical significance threshold at an interim analysis and that its final progression-free survival readout for patients with squamous disease is expected this year. A separate global trial, HARMONi-7, is testing ivonescimab alone against Keytruda in patients with high PD-L1 levels.
Trial sponsors often cover the study drug, but patients should ask about travel, time off work, and any costs their insurance may not pay. Obtaining an unapproved cancer drug outside a regulated study carries safety risks and should not be attempted without an oncologist's guidance.
Anyone currently on immunotherapy should report new symptoms promptly. Coughing up blood, severe shortness of breath, or chest pain requires emergency care. No one should stop or switch a current treatment based on these results.
The next U.S. milestone is Nov. 14, 2026, the FDA's target date for Summit's application to approve ivonescimab with chemotherapy for EGFR-mutated lung cancer that has progressed after treatment with a third-generation EGFR-targeted pill such as osimertinib. That decision covers a different patient group than HARMONi-2. No results date has been announced for HARMONi-7.
The HARMONi-2 survival data are the strongest evidence yet that ivonescimab can outperform Keytruda, but so far only in patients treated in China. For U.S. families, the practical step is asking about testing and trial eligibility while global results are pending.
Key Questions Answered
What did HARMONi-2 show? Patients with PD-L1-positive advanced lung cancer lived a median of 30.8 months on ivonescimab, compared with 22.6 months on Keytruda, a 27% lower risk of death.
Is ivonescimab available in the United States? No. It is approved in China but not by the FDA. U.S. patients can currently receive it only through a clinical trial.
Why does it matter that the trial was done only in China? Results from one region may not fully apply to U.S. patients, whose backgrounds and care practices can differ. Global trials are underway to test the drug more broadly.
Is ivonescimab safer than Keytruda? Not clearly. Serious treatment-related side effects were more common with ivonescimab, 29.9% versus 21.6%, although patients also stayed on it longer.
Who might benefit most? The largest apparent benefit was in patients with high PD-L1 levels, but the subgroup results were descriptive and not designed to prove a benefit.
How can patients find a trial? Ask an oncologist about eligibility and search ClinicalTrials.gov for ivonescimab studies that are currently recruiting. Some listed U.S. sites for HARMONi-3 are no longer enrolling.
When could the FDA act on ivonescimab? The FDA's target date is Nov. 14, 2026, for a separate application covering EGFR-mutated lung cancer that progressed after targeted therapy.
