PD-1/VEGF Bispecific Antibody Ivonescimab Extends Survival by 2.7 Months in EGFR Lung Cancer Phase 3 Trial
Final results show that adding the bispecific antibody to chemotherapy improved overall survival in EGFR-mutant lung cancer that progressed after targeted therapy.
EGFR-mutant non-small cell lung cancer (NSCLC) responds well to targeted drugs (EGFR-TKIs), but resistance eventually develops, and options afterward are limited. The HARMONi-A investigators published in JAMA the final overall survival results of a phase 3 trial adding ivonescimab, a bispecific antibody that simultaneously targets the immune checkpoint PD-1 and the angiogenic factor VEGF, to chemotherapy.
Placebo-controlled phase 3 trial at 55 sites in China
A total of 322 adults with non-squamous NSCLC that had progressed after EGFR-TKI treatment were split 1:1 to receive pemetrexed and carboplatin plus either ivonescimab (20 mg/kg) or placebo for 4 cycles, followed by maintenance therapy. The primary endpoint was progression-free survival (PFS) by independent review, and an improvement had already been confirmed in an earlier analysis. This report covered overall survival (OS), a key secondary endpoint tested hierarchically.
At a median follow-up of 32.5 months, median overall survival was 16.8 months versus 14.1 months, with a significant hazard ratio of 0.74. The 30-month survival rate was 29.1% versus 18.4%. On the other hand, grade 3 or higher adverse events during treatment were more frequent, at 67.1% in the ivonescimab group and 54.7% in the placebo group.
Significance and limitations
It is significant that a drug combining immuno-oncology and anti-angiogenesis mechanisms in one molecule also showed a survival benefit. However, the difference in median survival is 2.7 months, and toxicity increased. Only Chinese patients took part, and the control group received chemotherapy alone, so its position relative to other recent second-line treatments and its effect in other ethnic groups need separate confirmation.
- Median overall survival 16.8 vs 14.1 months, hazard ratio 0.74 (key secondary endpoint)
- Primary endpoint was independently reviewed progression-free survival; 322 patients, placebo-controlled double-blind phase 3 trial
- Grade 3 or higher adverse events increased: 67.1% vs 54.7%
Limitations This was a single-country trial in China compared only with chemotherapy alone, so the effect relative to other second-line treatments and generalizability across ethnic groups are unconfirmed.
Original research
- HARMONi-A Study Investigators · HARMONi-A investigators (55 sites in China). Bispecific Antibody Ivonescimab Added to Chemotherapy in EGFR-Variant Non-Small Cell Lung Cancer: The HARMONi-A Randomized Clinical Trial. JAMA. DOI: 10.1001/jama.2026.7745
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