Relapsed / Refractory · Phase III double-blind placebo-controlled; N=438; EGFR-mutated stage IIIB/IIIC or IV nonsquamous NSCLC after third-generation EGFR-TKI. Ivonescimab + pemetrexed/carboplatin vs placebo + chemotherapy. Dual primary endpoints PFS and OS. · Median PFS 6.8 vs 4.4 months

HARMONi

Primary setting: Relapsed / Refractory · Disease extent: Advanced / metastatic · Prior-treatment context: Relapsed / refractory or previously treated population; see trial-specific eligibility

Clinical question: Does ivonescimab plus pemetrexed/carboplatin improve outcomes over chemotherapy alone after progression on a third-generation EGFR-TKI?

Median PFS 6.8 vs 4.4 months; HR 0.52 (95% CI 0.41–0.66; P<0.0001). Median OS 16.8 vs 14.0 months; HR 0.79 (95% CI 0.62–1.01). · Registry:

Design, population and treatment

Phase III double-blind placebo-controlled; N=438; EGFR-mutated stage IIIB/IIIC or IV nonsquamous NSCLC after third-generation EGFR-TKI. Ivonescimab + pemetrexed/carboplatin vs placebo + chemotherapy. Dual primary endpoints PFS and OS.

Key efficacy outcome

6.8 · intervention

4.4

6.8 · comparator

Not calculable from median PFS.

Serious treatment-related AEs 28% vs 15%; grade 3–4 cytopenias common; treatment-related deaths four vs five.

Safety and absolute effect

Median PFS (months)

https://pubmed.ncbi.nlm.nih.gov/42636833/

Interpretation and limitations

Current-practice context · 14 November 2026: Primary publication/abstract and trial identifier checked. Guideline-level current-practice mapping was not established in this publication-led batch; no NCCN citation provenance is claimed. Where detailed QoL, follow-up or toxicity data were not present in the retrieved abstract, they are not inferred.

Primary source

Primary publication · DOI: 10.1016/S1470-2045(26)00282-2