Multicenter phase 3 trial of addition of ivonescimab to chemotherapy in EGFR-variant NSCLC: final overall survival results from HARMONi-A

Patients with EGFR gene variant nonsquamous non-small cell lung cancer (NSCLC) who have disease progression after EGFR-TKI therapy have limited treatment options. The phase 3 HARMONi-A trial, at 55 centers in China, evaluated addition of the bispecific PD-1 and VEGFR targeting antibody ivonescimab to chemotherapy for these patients. Final overall survival (OS) results from the trial have now been published. A total of 322 adult patients with locally advanced or metastatic EGFR-variant nonsquamous NSCLC who had received prior EGFR-TKI therapy were enrolled. Patients were randomized 1:1 to receive ivonescimab (20 mg/kg; n=161) or placebo (n=161) plus pemetrexed-carboplatin chemotherapy once every 3 weeks for 4 cycles, followed by maintenance therapy. During a median follow-up of 32.5 months, ivonescimab plus chemotherapy improved OS compared with chemotherapy alone (median survival 16.8 versus 14.1 months; sHR 0.74; p=0.02). Estimated 30-months survival rates were 29.1% versus 18.4%. Grade 3 or higher treatment-emergent adverse events occurred in 67.1% and 54.7% of patients receiving ivonescimab and placebo, respectively. The authors conclude that ivonescimab plus chemotherapy provided a statistically significant and clinically meaningful improvement in OS with an acceptable safety profile in patients with EGFR-variant NSCLC after EGFR-TKI therapy.