Background
Phase III RCT (HARMONI-A); N=322 EGFR-variant advanced/metastatic NSCLC (stage IIIB/IIIC/IV) progressing after EGFR-TKI (including 3rd-gen, e.g. osimertinib); double-blind, China.
Interventions and follow up
Arm A: Ivonescimab 20 mg/kg IV + pemetrexed 500 mg/m² IV + carboplatin AUC5 IV, every 3 weeks
Arm B: Placebo + pemetrexed 500 mg/m² IV + carboplatin AUC5 IV, every 3 weeks
Primary endpoint: PFS
mFollow up: 7.9mo
Arm B: Placebo + pemetrexed 500 mg/m² IV + carboplatin AUC5 IV, every 3 weeks
Primary endpoint: PFS
mFollow up: 7.9mo
Results
mPFS: 7.1 vs 4.8mo, HR 0.46, 95% CI 0.34–0.62, P<.001
mOS: 17.1 vs 14.5mo, HR 0.80, 95% CI 0.59–1.08 (interim)
ORR: 50.6% vs 35.4%
mOS: 17.1 vs 14.5mo, HR 0.80, 95% CI 0.59–1.08 (interim)
ORR: 50.6% vs 35.4%
Adverse events
Hematologic (Arm A vs B):
Neutrophil decreased: 31.1% vs 19.3%
WBC decreased: 20.5% vs 16.8%
Platelet decreased: 16.1% vs 12.4%
Anemia: 15.5% vs 14.3%
Neutrophil decreased: 31.1% vs 19.3%
WBC decreased: 20.5% vs 16.8%
Platelet decreased: 16.1% vs 12.4%
Anemia: 15.5% vs 14.3%
Conclusions
Ivonescimab plus chemotherapy significantly improved PFS over chemotherapy alone in EGFR-TKI–treated advanced NSCLC, with a tolerable safety profile.
Key Limitations
China-only population (generalizability); short follow-up; OS immature/not significant; PFS surrogate endpoint.
Clinical Context
Ivonescimab (PD-1/VEGF bispecific) is approved in China; not yet FDA/EMA-approved for this indication. Supports anti-angiogenic + chemo strategies after TKI failure; awaiting confirmatory global/OS data before ESMO incorporation.
References