---
title: Ivonescimab Beats Keytruda on Overall Survival in First Head-to-Head Lung Cancer Trial
description: A Phase III trial found ivonescimab, from China's Akeso, beat Merck's Keytruda on overall survival in first-line lung cancer. But the trial was China-only.
author: Darie Nani (Editor-in-Chief)
updated: 2026-09-13T09:16:33.777Z
canonical: https://www.sovereignmagazine.com/article/ivonescimab-beats-keytruda-overall-survival-harmoni-2
categories: Markets
content_type: Analysis
region: Global
publication: Sovereign Magazine
schema_type: Article
---

Ivonescimab, a cancer drug made by China's Akeso, kept patients with advanced lung cancer alive a median of 30.8 months, against 22.6 months for those on Merck's Keytruda, in a Phase III trial that put the two drugs directly against each other. Researchers presented the finding at the 2026 World Conference on Lung Cancer as a late-breaking result from the HARMONi-2 trial. It is the first time any single drug has beaten Keytruda on overall survival, head-to-head, in first-line PD-L1-positive advanced non-small-cell lung cancer, the setting where Keytruda has been the standard for nearly a decade.

## Patients on Ivonescimab Lived About Eight Months Longer

The gap between the two arms was 8.2 months of median survival. The hazard ratio was 0.73, with a 95% confidence interval of 0.57 to 0.95 and a p-value of 0.009, based on 234 deaths as of the August 20, 2026 data cutoff. Those numbers clear the bar for statistical significance, meaning the survival edge is unlikely to be a fluke of the sample.

## Overall Survival Was a Secondary Goal in the Trial

HARMONi-2 was designed to test progression-free survival, how long patients go before their cancer worsens, and it met that target in 2024. On that primary endpoint, patients on ivonescimab went a median of 11.14 months before progression, against 5.82 months on Keytruda, a hazard ratio of 0.51 that researchers reported at the 2024 conference and published in the Journal of Thoracic Oncology. Overall survival was a key secondary endpoint. Regulators give a secondary result less weight than the endpoint a trial was built to prove: it is persuasive, but it is not what HARMONi-2 was primarily powered to show.

## Every Patient Was Treated in China

HARMONi-2 enrolled 398 patients across 55 centers, all of them in China, and Akeso sponsored it. That is the biggest reason oncologists are not yet treating the question as settled. Dr. John Heymach of MD Anderson, one of the most prominent independent voices in lung cancer, called the earlier ivonescimab data striking but raised three reservations that still stand: the trial enrolled only Chinese patients, Keytruda given on its own may not match the current standard of care in every region, and confirmatory trials outside China are [essential before drawing broad conclusions](https://ascopost.com/issues/november-25-2024-supplement-conference-highlights-2024-wclc/harmoni-2-ivonescimab-outperforms-pembrolizumab-as-first-line-treatment-in-nsclc/). A US FDA official from the agency's biologics center has [cautioned more bluntly](https://friendsofcancerresearch.org/news/pink-sheet-first-in-china-trials-may-be-counterproductive-for-sponsors-us-fda-cber-official-says/) that trials run first and only in China can work against sponsors seeking American approval.

## The Global Trial Missed Its First Target

HARMONi-3, the larger global Phase III study testing ivonescimab plus chemotherapy in a broader patient population, missed its progression-free-survival goal at an interim analysis in 2026. That is the trial built to answer exactly the question Heymach raised, whether the China result holds up in a wider, more international setting, and its first analysis did not produce the same result. That makes HARMONi-3 the main reason for caution about whether the China result holds up elsewhere.

## Keytruda Sells Over $30 Billion a Year, and Its Protection Is Starting to Fade

Keytruda is the world's top-selling prescription drug, with more than $30 billion in annual sales, and lung cancer is its single largest use. Pembrolizumab, its generic name, has been a first-line standard for PD-L1-positive NSCLC since the KEYNOTE-024 and KEYNOTE-042 trials in 2016 and 2019. Merck's main US patent protection runs to the mid-2030s, but the franchise's market exclusivity begins to erode toward the end of this decade, with biosimilar competition expected. A drug with a credible survival advantage arrives just as that window opens, which is why analysts treat a China-only secondary endpoint as a strategic event, not a footnote.

## The Nearest US Decision Is for a Different Use

Ivonescimab is a bispecific antibody, a single molecule that blocks both PD-1 and VEGF, two targets that today's therapies usually hit with separate drugs. China's regulator approved it in April 2025 for first-line PD-L1-positive NSCLC. It is not approved in the United States or the European Union. Summit Therapeutics holds the license for the US, EU, Japan and Latin America, and the nearest US decision does not turn on HARMONi-2 at all: the FDA has accepted a Biologics License Application for ivonescimab in a different indication, EGFR-mutated NSCLC after TKI therapy in combination with chemotherapy, backed by global-trial data, with a decision date of November 14, 2026. An approval in the first-line setting HARMONi-2 studied would require the Western confirmatory data those experts are asking for.

## FAQ

**Q: What did the HARMONi-2 trial find?**
In first-line PD-L1-positive advanced non-small-cell lung cancer, patients on ivonescimab lived a median of 30.8 months against 22.6 months on Keytruda (hazard ratio 0.73, p=0.009), and earlier had a longer time before their cancer progressed. It is the first randomized head-to-head trial in which a drug beat Keytruda on overall survival.

**Q: Is ivonescimab better than Keytruda?**
In this one trial, run entirely in China with overall survival as a secondary endpoint, it beat Keytruda on both survival measures. Independent experts, including John Heymach, say confirmatory data in Western patients is needed before that result can be generalized, and the broader global trial, HARMONi-3, missed its main goal at an interim look.

**Q: Is ivonescimab approved in the US, and when might it be?**
Not yet. China approved it in April 2025. In the US, the FDA is due to decide by November 14, 2026 on a separate indication, EGFR-mutated NSCLC after TKI therapy with chemotherapy. Approval in the first-line setting HARMONi-2 tested would need Western trial data.

**Q: What is ivonescimab and how does it work?**
It is a bispecific antibody that blocks both PD-1 and VEGF, two cancer targets, in a single molecule.