KEY TAKEAWAYS
- The HARMONi-2 phase 3 trial aimed to compare the efficacy and safety of ivonescimab and pembrolizumab as 1L treatment in patients with PD-L1 positive NSCLC.
- The primary endpoint was PFS.
- Researchers noticed Ivonescimab significantly improved PFS over pembrolizumab in patients with PD-L1-positive advanced NSCLC.
Non-small cell lung cancer (NSCLC) is a leading cause of cancer-related mortality globally. Immune checkpoint inhibitors, particularly those targeting the programmed death-1 (PD-1) pathway, have revolutionized the treatment landscape for advanced NSCLC.
However, a significant proportion of patients do not achieve durable responses. Ivonescimab is a novel bispecific antibody targeting both PD-1 and vascular endothelial growth factor (VEGF), demonstrating promising results in earlier-phase studies.
Caicun Zhou and the team aimed to compare the efficacy and safety of ivonescimab with pembrolizumab, a standard-of-care PD-1 inhibitor, as a first-line (1L) treatment for patients with PD-L1-positive advanced NSCLC.
The study was a randomized, controlled trial conducted across 55 centers. Eligible patients with untreated locally-advanced or metastatic NSCLC, ECOG performance status 0-1, PD-L1 positive (tumor proportion score [TPS] ≥1%), but negative for EGFR mutations or ALK rearrangements were randomized 1:1 to receive either ivonescimab 20 mg/kg or pembrolizumab 200 mg every 3 weeks.
Randomization was stratified by histology, clinical stage, and PD-L1 expression level. The primary endpoint was progression-free survival (PFS) as assessed by a blinded independent radiographic review committee using RECIST v1.1 criteria. Secondary endpoints included overall survival (OS), investigator-assessed PFS, objective response rate (ORR), duration of response (DoR), disease control rate (DCR), and safety.
Between November 2022 and August 2023, 398 patients were randomized to receive either ivonescimab (n=198) or pembrolizumab (n=200). At the pre-planned interim analysis, the median PFS was significantly longer with ivonescimab compared to pembrolizumab (11.14 months vs. 5.82 months; stratified HR, 0.51; 95% CI, 0.38-0.69; P<0.0001).
The PFS benefit of ivonescimab was observed across various subgroups, including those defined by histology, PD-L1 expression levels, and presence of liver or brain metastases. Ivonescimab exhibited a manageable safety profile, with no new safety signals identified.
The incidence of treatment-related serious adverse events (TRSAEs) was 20.8% with ivonescimab and 16.1% with pembrolizumab. Grade ≥3 immune-related adverse events (irAEs) were observed in 7.1% and 8.0% of patients in the ivonescimab and pembrolizumab arms, respectively.
The study demonstrated that ivonescimab provides a statistically significant and clinically meaningful improvement in PFS compared to pembrolizumab in patients with PD-L1-positive advanced NSCLC. Ivonescimab also showed a manageable safety profile. These findings support ivonescimab as a promising new 1L treatment option for this patient population.
The trial was sponsored by Akeso.
Source: https://cattendee.abstractsonline.com/meeting/20598/presentation/3194
Clinical Trial: https://clinicaltrials.gov/study/NCT05499390
Zhou C, Chen J, Wu L, et al. (2024). “Phase 3 study of ivonescimab (AK112) vs pembrolizumab as first-line treatment for PD-L1-positive advanced NSCLC: primary analysis of HARMONi-2.” Presented at: World Conference on Lung Cancer (WCLC); September 8, 2024; Singapore.
