- 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 (BICR) and overall survival
- Effect
- PFS HR 0.52 (0.41–0.66); OS HR 0.79 (0.62–1.01)
HARMONi randomised 438 patients with advanced non-squamous EGFR-mutated NSCLC progressing after a third-generation EGFR-TKI to ivonescimab, a PD-1/VEGF bispecific antibody, or placebo, each with pemetrexed and carboplatin. It was double-blind, 70% of patients were Asian, and it was published in The Lancet Oncology in September.
Median progression-free survival was 6.8 versus 4.4 months (HR 0.52, 95% CI 0.41 to 0.66). Median overall survival was 16.8 versus 14.0 months (HR 0.79, 0.62 to 1.01), which did not reach significance. Serious treatment-related adverse events occurred in 28% versus 15%.
The progression-free gain is real and the population is highly relevant to India, where EGFR-mutated lung cancer is common. But without a clear survival advantage and with more serious toxicity, it is an option to discuss rather than a new standard. Its regulatory status with CDSCO is not stated in this record.
- After osimertinib progression, rebiopsy for resistance mechanisms before choosing therapy.
- Platinum-pemetrexed remains the backbone.
- Discuss the PFS gain and the uncertain survival benefit with patients.
- Monitor for bleeding and thrombosis with VEGF-targeting agents.
Why it matters
Post-osimertinib options are limited, and this adds one with a clear PFS gain.
Don't overread it
The overall survival difference did not reach statistical significance.
The statistics, in plain English
The overall survival interval (0.62 to 1.01) just crosses 1, so a survival benefit is possible but not proven. Serious adverse events were nearly double, which matters when survival gain is uncertain.
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