PD-L1-positive locally advanced or metastatic NSCLC without EGFR or ALK alterations
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Ivonescimab | 20 mg/kg | IV | Every 3 weeks |
Comparator arm: pembrolizumab 200 mg every 3 weeks.
Ivonescimab versus pembrolizumab for PD-L1-positive non-small cell lung cancer (HARMONi-2): a randomised, double-blind, phase 3 study in China
Xiong A, Wang L, Chen J, Wu L, Liu B, Yao J, et al. Lancet. 2025. 405:839-849
- Study type
- Clinical trial
- Study name
- HARMONi-2
- Phase
- Phase 3
- Design
- Randomised, double-blind trial at 55 hospitals in China, 1:1 ratio
- Sample size
- 398 patients
- Source
- Lancet · 2025
- Trial registration
- NCT05499390
In plain words
In patients with advanced PD-L1-positive lung cancer, the two-way drug ivonescimab, compared directly with pembrolizumab, almost doubled the time the disease was kept under control. Data on length of life (overall survival) from this study have not yet been published.
Key results
11.1 vs 5.8 months
Median progression-free survival
Stratified HR 0.51 (95% CI 0.38–0.69); one-sided p<0.0001
HR 0.54
Progression-free survival – PD-L1 1 to 49%
95% CI 0.37–0.78
HR 0.48
Progression-free survival – PD-L1 50% or more
95% CI 0.29–0.79
29% vs 16%
Grade 3 or higher treatment-related adverse events
Drugs in this study:Pembrolizumab (Keytruda)
Dose and schedule cards
HARMONi-2: ivonescimab monotherapy
PD-L1-positive locally advanced or metastatic NSCLC without EGFR or ALK alterationsCycle length: Every 3 weeksOn the page “Ivonescimab: a dual-action antibody helped people with lung cancer live longer” · Ivonescimab trial regimens (investigational; not approved by the FDA or EMA)
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
Treatment arms and regimens
1Ivonescimab (198 patients)
Ivonescimab 20 mg/kg IV infusion every 3 weeks. The maximum treatment duration is not given in the available sources.
2Pembrolizumab (200 patients)
Pembrolizumab 200 mg IV infusion every 3 weeks. The maximum treatment duration is not given in the available sources.
Source of the regimen details: Abstract of the published paper (Lancet 2025; PMID 40057343) and ClinicalTrials.gov NCT05499390; the full text was not available in PMC, and the maximum treatment duration, premedication and dose-modification rules are not given in these sources.
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Adults aged 18 years or older with locally advanced or metastatic NSCLC (stage IIIB/C or IV) with positive PD-L1 expression (subgroups: TPS 1 to 49% and 50% or more), without a sensitising EGFR mutation or ALK translocation, ECOG performance status 0 or 1, no prior systemic therapy for advanced disease, measurable disease and adequate organ function; 55 hospitals in China. Key exclusion criteria: any small-cell component, active central nervous system metastases, active autoimmune disease requiring systemic treatment in the past 2 years, myocardial infarction, unstable angina or congestive heart failure in the past 12 months, active hepatitis B or C. Randomisation was stratified by histology, clinical stage and PD-L1 expression.
Endpoints
Primary endpoint: progression-free survival by blinded independent radiology review committee (RECIST 1.1) in the intention-to-treat population.
Safety and side effects
Grade 3 or higher treatment-related adverse events occurred in 58 patients (29%) in the ivonescimab group and 31 patients (16%) in the pembrolizumab group. Grade 3 or higher immune-related adverse events: 14 of 197 (7%) versus 16 of 199 (8%). In patients with squamous carcinoma, grade 3 or higher treatment-related adverse events were comparable between the two groups. Rates of bleeding and treatment discontinuation are not given in the abstract.
Clinical significance and place in guidelines
The first phase 3 trial in which a drug significantly improved progression-free survival in a head-to-head comparison with single-agent pembrolizumab; according to the manufacturer, the basis for the approval of ivonescimab in China for first-line treatment of PD-L1-positive lung cancer. The lack of overall survival data and the fact that the study was conducted only in China are its main limitations.
Limitations
China only; primary endpoint progression-free survival at an interim analysis; overall survival data were immature at the time of publication.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.