# HARMONi-2

Source: https://onco.cc/trials/harmoni-2/  
OnCo record `harmoni-2` (Trial). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

The first head-to-head trial in which a new drug beat Keytruda, in China; a survival benefit followed in 2026.

## Summary

HARMONi-2, trial NCT05499390 sponsored by Akeso and reported in 2024, was the first head-to-head trial in which a new drug beat pembrolizumab, comparing the PD-1 by VEGF bispecific ivonescimab with pembrolizumab as first-line monotherapy for PD-L1-positive advanced non-small-cell lung cancer in China. It randomised 398 patients, met its primary progression-free survival endpoint by independent review with a substantial improvement, and in 2026 Akeso and Summit reported a statistically significant overall survival benefit. OnCo links it to PD-1 and VEGF as targets, to Michelle Xia, Qing Zhou and Caicun Zhou, and to HARMONi-A. It was a single-country trial and the global HARMONi-3 interim analysis did not reproduce the progression-free survival margin, so whether Western regulators accept the result rests on HARMONi-3 and HARMONi-7. Ivonescimab has its own page.

## Fields

- Kind: Trial
- Status: positive
- Last checked: 2026-09-06
- Registry id: NCT05499390
- Phase: 3
- Setting: First-line PD-L1-positive (TPS ≥1%) advanced NSCLC in China: ivonescimab vs pembrolizumab monotherapy
- Sponsor: Akeso
- Enrolled: 398
- Result: PFS HR 0.51; OS statistically significant (2026 announcement).
- Outcomes: Progression-free survival (IRRC): Ivonescimab 11.1 months vs Pembrolizumab 5.8 months, HR 0.51
- Replication: Single-country (China) trial; OS immature. The global HARMONi-3 interim did not reproduce the PFS margin, so replication outside China is unresolved.

## Sources

- ClinicalTrials.gov NCT05499390: https://clinicaltrials.gov/study/NCT05499390
- Summit press release (2026 OS): https://smmttx.com/news/press-releases/news-details/2026/Ivonescimab-Monotherapy-Demonstrates-Statistically-Significant-Overall-Survival-Benefit-Compared-to-Pembrolizumab-Monotherapy-in-PD-L1-Positive-Advanced-NSCLC-in-HARMONi-2-Study-Conducted-by-Akeso-in-China/default.aspx

## Connected records

- cancers: [Lung cancer (all types)](https://onco.cc/cancers/lung-cancer/), [Non-small-cell lung cancer](https://onco.cc/cancers/nsclc/), [PD-L1-high non-small-cell lung cancer without a driver mutation](https://onco.cc/cancers/pdl1-high-nsclc/)
- technologies: [Bispecific antibodies](https://onco.cc/technologies/bispecific-antibody/), [Immune checkpoint inhibitors](https://onco.cc/technologies/checkpoint-inhibitor/)
- targets: [PD-1](https://onco.cc/targets/pd1/), [VEGF / VEGFR](https://onco.cc/targets/vegf/)
- drugs: [Ivonescimab](https://onco.cc/drugs/ivonescimab/), [Pembrolizumab](https://onco.cc/drugs/pembrolizumab/)
- companies: [Akeso](https://onco.cc/companies/akeso/)
- people: [Caicun Zhou](https://onco.cc/people/zhou-caicun/), [Michelle Xia (Xia Yu)](https://onco.cc/people/xia-michelle/), [Qing Zhou](https://onco.cc/people/qing-zhou/)
- key papers: [HARMONi-2: ivonescimab, a PD-1 x VEGF bispecific, beats pembrolizumab head-to-head in PD-L1-positive lung cancer](https://onco.cc/key-papers/paper-harmoni-2-lancet-2025/)
- trials: [HARMONi-A](https://onco.cc/trials/harmoni-a/)
- roadmaps: [Global access and affordability roadmap: essential medicines and generics → biosimilars and frugal trials → reliance, pooling and homegrown innovation](https://onco.cc/roadmaps/global-access-roadmap/)

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