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Using 22C3 Anti-PD-L1 Antibody Concentrate on Biopsy and Cytology Samples from Non-small Cell Lung Cancer Patients
Published on: September 25, 2018
Ivonescimab versus pembrolizumab for PD-L1-positive non-small cell lung cancer (HARMONi-2): a randomised,
Anwen Xiong1, Lei Wang1, Jianhua Chen2
1Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Background:
Ivonescimab is a bispecific antibody against programmed cell death protein 1 and vascular endothelial growth factor, yielding promising clinical outcomes for patients with advanced non-small cell lung cancer in early-phase studies. We compared the efficacy and safety of ivonescimab with pembrolizumab in patients with programmed cell death ligand-1 (PD-L1)-positive advanced non-small cell lung cancer.
Methods:
HARMONi-2 is a randomised, double-blind, phase 3 trial across 55 hospitals in China. Eligible patients were aged 18 years or older and had locally advanced or metastatic PD-L1-positive non-small cell lung cancer without sensitising epidermal growth factor receptor mutations or anaplastic lymphoma kinase translocations and an Eastern Cooperative Oncology Group performance-status of 0 or 1. Patients were randomly assigned (1:1) to receive 20 mg/kg ivonescimab or 200 mg pembrolizumab intravenously every 3 weeks. Randomisation was stratified by histology, clinical stage, and PD-L1 expression. The primary endpoint was progression-free survival (PFS) assessed by a masked independent radiographic review committee per RECIST v1.1 in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT05499390; recruitment is complete, with the trial ongoing and final analysis to be reported later.
Findings:
Between Nov 9, 2022, and Aug 26, 2023, 398 (45%) of 879 screened patients were randomly assigned to receive ivonescimab (n=198) or pembrolizumab (n=200). At the preplanned interim analysis, median PFS was significantly longer with ivonescimab than with pembrolizumab (11·1 vs 5·8 months; stratified hazard ratio [HR] 0·51 [95% CI 0·38-0·69]; one-sided p<0·0001). The PFS benefit of ivonescimab over pembrolizumab was broadly consistent within prespecified subgroups, including patients with PD-L1 tumour proportion score (TPS) 1-49% (HR 0·54 [95% CI 0·37-0·78]) and PD-L1 TPS of 50% of higher (HR 0·48 [0·29-0·79]). Grade 3 or higher treatment-related adverse events occurred in 58 (29%) patients with ivonescimab and 31 (16%) patients with pembrolizumab. Immune-related adverse events of grade 3 or higher were observed in 14 (7%) of 197 patients on ivonescimab and 16 (8%) of 199 patients on pembrolizumab. Ivonescimab demonstrated a manageable safety profile in patients with both squamous and non-squamous non-small cell lung cancer. In patients with squamous cell carcinoma, grade 3 or higher treatment-related adverse events were comparable between the two groups.
Interpretation:
Ivonescimab significantly improved PFS compared with pembrolizumab in previously untreated patients with advanced PD-L1 positive non-small cell lung cancer. Therefore, ivonescimab might represent another treatment option in the first-line setting for PD-L1-positive advanced non-small cell lung cancer.
Funding:
Akeso Biopharma.
Insights
Ivonescimab significantly improved progression-free survival (PFS) in patients with advanced non-small cell lung cancer compared to pembrolizumab. This bispecific antibody offers a promising new first-line treatment option for PD-L1-positive lung cancer.
Area of Science:
- Oncology
- Immunotherapy
- Clinical Trials
Background:
- Ivonescimab is a novel bispecific antibody targeting PD-1 and VEGF.
- Early studies showed promising outcomes for ivonescimab in advanced non-small cell lung cancer (NSCLC).
- This study compares ivonescimab to pembrolizumab in PD-L1-positive advanced NSCLC.
Purpose of the Study:
- To compare the efficacy and safety of ivonescimab versus pembrolizumab.
- To evaluate progression-free survival (PFS) as the primary endpoint.
- To assess treatment outcomes in previously untreated advanced NSCLC patients.
Main Methods:
- A randomized, double-blind, phase 3 trial (HARMONi-2) conducted in China.
- 398 patients with PD-L1-positive advanced NSCLC were randomized (1:1) to ivonescimab or pembrolizumab.
- Primary endpoint was PFS assessed by independent review.
Main Results:
- Median PFS was significantly longer with ivonescimab (11.1 months) versus pembrolizumab (5.8 months).
- The hazard ratio for PFS was 0.51, favoring ivonescimab (p<0.0001).
- Grade 3+ treatment-related adverse events were higher with ivonescimab (29%) than pembrolizumab (16%), but manageable.
Conclusions:
- Ivonescimab demonstrated a significant PFS benefit over pembrolizumab in first-line advanced PD-L1-positive NSCLC.
- Ivonescimab shows a manageable safety profile.
- Ivonescimab represents a potential new first-line treatment option for this patient population.
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