- Design
- Phase 3, randomised, double-blind, placebo-controlled
- Population
- 438 patients with EGFR-mutated NSCLC after third-generation TKI progression
- Primary outcome
- Progression-free survival and overall survival
- Effect
- PFS 6.8 vs 4.4 months, HR 0.52 (0.41–0.66); OS HR 0.79 (0.62–1.01)
HARMONi was a double-blind, placebo-controlled phase 3 trial at 114 centres in Asia, Europe and North America. It enrolled 438 patients with advanced non-squamous EGFR-mutated NSCLC whose disease had progressed on a third-generation EGFR TKI, randomised to ivonescimab, a PD-1 and VEGF bispecific antibody, or placebo, each with pemetrexed and carboplatin.
Median progression-free survival was 6.8 against 4.4 months (HR 0.52, 95% CI 0.41–0.66). Median overall survival was 16.8 against 14.0 months (HR 0.79, 0.62–1.01), which did not reach statistical significance. Serious treatment-related adverse events were more frequent with ivonescimab (28% vs 15%), including more grade 3–4 thrombocytopenia.
After osimertinib, platinum–pemetrexed is the usual next step and immunotherapy has disappointed in this setting. HARMONi suggests a dual-target approach adds progression-free time, but the overall survival result leaves its value open. Regulatory status and access in India are not established here.
- Platinum–pemetrexed remains the standard after third-generation EGFR TKI progression.
- Ivonescimab added about 2.4 months of median progression-free survival but did not significantly improve overall survival.
- Serious treatment-related adverse events were nearly doubled; monitor platelets closely.
- Rebiopsy or liquid biopsy at progression still guides targeted options first.
Why it matters
Post-osimertinib disease is a growing population with few effective options.
Don't overread it
Overall survival, a co-primary endpoint, did not reach significance; progression-free survival alone does not establish a survival benefit.
The statistics, in plain English
An overall survival hazard ratio of 0.79 with an interval reaching 1.01 means the data fit anything from a 38% reduction in death to no effect. Further follow-up may clarify it.
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