Multicenter phase 3 trial of ivonescimab plus chemotherapy for non-small cell lung cancer with EGFR variant

For patients with non-small cell lung cancer (NSCLC) whose disease progresses while receiving EGFR-TKI therapy optimal treatment options remain limited. Ivonescimab is a bispecific antibody targeting PD-1 and VEGF. The multicenter phase 3 HARMONi-A trial in China compared ivonescimab plus chemotherapy versus placebo plus chemotherapy for patients with advanced or metastatic NSCLC with EFGR variant who experienced resistance while receiving EGFR-TKI treatment. In this trial of 322 patients, ivonescimab plus chemotherapy significantly improved progression-free survival compared with placebo plus chemotherapy. Median progression-free survival was 7.06 months with ivonescimab versus 4.80 months with placebo (HR 0.46; p<0.001). Grade 3 or higher treatment-emergent adverse events occurred in 61.5% of patients in the ivonescimab group and 49.1% of patients in the placebo group. The authors conclude that ivonescimab plus chemotherapy significantly improved progression-free survival with a tolerable safety profile in patients with NSCLC who previously underwent EGFR-TKI treatment (visual abstract).