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Bispecific Antibody Ivonescimab Added to Chemotherapy in EGFR-Variant Non-Small Cell Lung Cancer: The HARMONi-A
, Wenfeng Fang1, Yuanyuan Zhao1
1Sun Yat-sen University Cancer Center, Guangzhou, China.
Importance:
Patients with epidermal growth factor receptor (EGFR) gene variant nonsquamous non-small cell lung cancer (NSCLC) who have disease progression after prior EGFR tyrosine kinase inhibitor (TKI) therapy have limited treatment options, creating a need for more effective subsequent therapies.
Objective:
To provide final overall results of a trial assessing whether adding ivonescimab (a bispecific antibody targeting programmed cell death protein 1 and vascular endothelial growth factor) to chemotherapy improves overall survival in this population.
Design, Setting, And Participants:
Randomized, double-blind, placebo-controlled phase 3 trial conducted at 55 sites in China. From January 25 to November 2, 2022, a total of 322 adult patients with locally advanced or metastatic EGFR-variant nonsquamous NSCLC who had received prior EGFR-TKI therapy were enrolled. The data cutoff date was April 12, 2025.
Interventions:
Patients were randomized 1:1 to receive ivonescimab (20 mg/kg; n = 161) or placebo (n = 161) plus chemotherapy with pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy.
Main Outcomes And Measures:
This final results report focuses on overall survival, the key secondary end point, tested in a hierarchical manner (the primary end point was progression-free survival assessed by an independent radiology review committee).
Results:
The 322 enrolled patients had a median age of 59.4 years, and 51.6% were female. During a median follow-up of 32.5 months, ivonescimab plus chemotherapy improved overall survival compared with chemotherapy alone (median survival, 16.8 months vs 14.1 months; stratified hazard ratio, 0.74; 95% CI, 0.58-0.95; P = .02). The absolute difference in median overall survival was 2.7 months. Estimated 30-month survival rates were 29.1% (95% CI, 22.1%-36.4%) with ivonescimab and 18.4% (95% CI, 12.8%-24.8%) with placebo. Grade 3 or higher treatment-emergent adverse events occurred in 67.1% and 54.7% of patients receiving ivonescimab and placebo, respectively.
Conclusions And Relevance:
Ivonescimab plus chemotherapy provided a statistically significant and clinically meaningful improvement in overall survival with an acceptable safety profile in patients with EGFR-variant NSCLC after EGFR-TKI therapy.
Trial Registration:
ClinicalTrials.gov Identifier: NCT05184712.
Insights
Adding ivonescimab to chemotherapy significantly improved overall survival for patients with EGFR-variant non-small cell lung cancer (NSCLC) after prior tyrosine kinase inhibitor (TKI) therapy, offering a new treatment option.
Area of Science:
- Oncology
- Medical Research
- Clinical Trials
Background:
- Patients with epidermal growth factor receptor (EGFR) gene variant nonsquamous non-small cell lung cancer (NSCLC) progressing after EGFR tyrosine kinase inhibitor (TKI) therapy have limited treatment options.
- There is a critical need for more effective subsequent therapies in this patient population.
Purpose of the Study:
- To report the final overall survival results of a phase 3 trial evaluating ivonescimab plus chemotherapy versus chemotherapy alone in patients with EGFR-variant nonsquamous NSCLC.
- To assess the efficacy and safety of ivonescimab as a subsequent therapy in this specific patient group.
Main Methods:
- A randomized, double-blind, placebo-controlled phase 3 trial (NCT05184712) enrolled 322 adult patients with locally advanced or metastatic EGFR-variant nonsquamous NSCLC who had prior EGFR-TKI therapy.
- Patients were randomized 1:1 to receive ivonescimab (20 mg/kg) or placebo, both combined with chemotherapy (pemetrexed and carboplatin) for 4 cycles, followed by maintenance therapy.
- Overall survival was the key secondary endpoint, analyzed hierarchically after progression-free survival.
Main Results:
- Ivonescimab plus chemotherapy demonstrated a statistically significant improvement in overall survival compared to chemotherapy alone (median survival: 16.8 months vs. 14.1 months; HR, 0.74; P=.02).
- The absolute difference in median overall survival was 2.7 months, with estimated 30-month survival rates of 29.1% for ivonescimab and 18.4% for placebo.
- Grade 3 or higher treatment-emergent adverse events occurred in 67.1% of patients receiving ivonescimab and 54.7% receiving placebo, indicating an acceptable safety profile.
Conclusions:
- The addition of ivonescimab to chemotherapy significantly improves overall survival in patients with EGFR-variant NSCLC who have progressed after EGFR-TKI therapy.
- Ivonescimab plus chemotherapy offers a clinically meaningful benefit with an acceptable safety profile, representing a valuable new treatment option for this population.
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