China Approves Ivonescimab with Chemotherapy for 2L+ EGFRm NSCLC Based on HARMONi-A Trial

Akeso Inc., a prominent biopharmaceutical company, announced on May 24, 2024, the receipt of marketing authorization from China's National Medical Products Administration (NMPA) for ivonescimab. This approval stems from positive results obtained in the HARMONi-A Phase III clinical trial, which evaluated ivonescimab combined with platinum-doublet chemotherapy in patients with epidermal growth factor receptor (EGFR)-mutated, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) who had previously been treated with EGFR tyrosine kinase inhibitors (TKIs).

HARMONi-A Study Overview

The HARMONi-A trial was conducted across multiple centers in China and compared the efficacy of ivonescimab plus chemotherapy against a placebo plus chemotherapy in this specific patient population. Notably, PD-1 monoclonal antibodies had previously failed in similar Phase III global clinical trials, highlighting the potential of ivonescimab's unique mechanism as a PD-1/VEGF bispecific antibody.

Separate from the HARMONi-2 trial, which involved NSCLC patients with tumors showing positive PD-L1 expression, the HARMONi-A trial focused exclusively on EGFR-mutated NSCLC patients.

Efficacy Results

The primary endpoint of progression-free survival (PFS) was significantly improved in the ivonescimab plus chemotherapy group, with a hazard ratio (HR) of 0.46, indicating a 54% reduction in the risk of disease progression compared to the placebo group. Specifically, median PFS was 7.1 months for ivonescimab plus chemotherapy versus 4.8 months for the placebo group. For patients who had previously been treated with a 3rd generation EGFR TKI, the hazard ratio was 0.48, signifying a 52% reduction in disease progression risk.

The overall survival (OS) data, while not fully mature, showed positive trends. After a median follow-up of 10.2 months, the hazard ratio was 0.72, and after 17.6 months, it was 0.80. The overall response rate (ORR) was also higher in the ivonescimab plus chemotherapy group at 50.6%, compared to 35.4% in the placebo group. The disease control rate (DCR) was 93.1% for ivonescimab plus chemotherapy versus 83.2% for the placebo group.

Safety Profile

Ivonescimab demonstrated a manageable safety profile with common treatment-related adverse events (TRAEs) including decreases in white blood cell count, anemia, and reductions in neutrophil and platelet counts. Treatment discontinuation due to adverse events was slightly higher in the ivonescimab group (5.6%) compared to the placebo group (2.5%). Grade 3 or higher immune-related adverse events occurred in 6.2% of patients receiving ivonescimab compared to 2.5% in the placebo group. Importantly, no TRAEs resulted in death in this study.

Future Prospects

The ongoing HARMONi trial extends the evaluation of ivonescimab plus chemotherapy to patients across North America, China, and Europe with a planned total enrollment of approximately 420 patients. This trial will include patients from the HARMONi-A study who had previously received a 3rd generation TKI.

Presentation and Publications

Dr. Li Zhang from Sun Yat-Sen University Cancer Center will present the HARMONi-A data at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. Additionally, a manuscript detailing the HARMONi-A results has been published in JAMA.

About Ivonescimab

Known as SMT112 in Summit's licensed territories and as AK112 in China and Australia, ivonescimab is a novel bispecific antibody that combines PD-1 blockade with anti-VEGF effects, showing higher binding affinity in the presence of both targets. This design aims to direct the antibody more effectively to tumor tissue, potentially enhancing its efficacy and safety profile.

Conclusion

Akeso Inc.'s advancement with ivonescimab marks a significant milestone in the treatment of EGFR-mutated NSCLC. The approval by the NMPA is a testament to the promising results from the HARMONi-A study, paving the way for improved therapeutic options for patients with this challenging form of lung cancer.

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