According to results from the phase 3 HARMONi-2 trial, ivonescimab showed a clinically meaningful and statistically significant improvement to progression-free survival (PFS) for patients with PD-L1–positive, advanced non-small cell lung cancer (NSCLC), when compared with pembrolizumab. 

These results were first presented by Caicun Zhou, MD, PhD, Shanghai Pulmonary Hospital, Shanghai, China, at the 2024 World Conference on Lung Cancer.

The HARMONi-2 trial enrolled 398 patients with locally advanced or metastatic NSCLC who were PD-L1–positive (with a tumor proportion score [TPS] ≥ 1%) but did not have EGFR mutations or ALK rearrangements. Patients were randomized on a 1-to-1 basis to receive either 20 mg/kg of ivonescimab (n = 198), or 200 mg of pembrolizumab (n = 200), every 3 weeks. Radnomization was stratified by histology (squamous vs non-squamous), clinical stage (IIIB/IIIC vs IV), and PD-L1 expression (TPS 1% to 49% vs TPS ≥ 50%). The primary end point of this study was PFS as assessed by a blinded, independent radiographic review committee. The secondary end points included overall survival (OS), investigator-assessed PFS, objective response rate (ORR), duration of response (DOR), disease control rate (DCR), and safety.

At the preplanned interim analysis, the media PFS with ivonescimab was 11.14 months vs 5.82 months with pembrolizumab (stratified hazard ratio [HR], 0.51; 95% confidence interval [CI}, 0.38 to 0.69; P < .0001). This benefit with ivonescimab was consistent across pre-specified subgroups. There were no new safety signals with ivonescimab identified. There were 20.8% of patients in the ivonescimab arm who experienced treatment-related serious adverse events, vs 16.1% of patients in the pembrolizumab arm. In the ivonescimab arm, 7.1% of patients ecperienced a grade ≥3 immune-related adverse event vs 8.0% in the pembrolizumab arm. Study authors noted that the safety profile was “very manageable” among patients with squamous cell carcinoma, where treatment-related serious adverse events occurred in 18.9% in the ivonescimab arm and 18.7% in the pembrolizumab arm. 

As Dr Zhou et al concluded, “The data support ivonescimab monotherapy as the new first-line treatment option for PD-L1 positive [advanced] NSCLC [patients].”

Source:

Zhou C, Chen J, Wu L, et al. 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 the 2024 World Conference on Lung Cancer. September 7-10, 2024; San Diego, CA. Abstract # PL02.04.