Dr Zhou on Frontline Ivonescimab vs Pembrolizumab in PD-L1+ Advanced NSCLC

“Progression-free survival was significantly improved, overall response rate was improved, and the disease control rate was also improved. When we look at safety profile, [ ivonescimab] is well tolerated.”

Caicun Zhou, MD, PhD, director, Department of Oncology, Shanghai Pulmonary Hospital, and director, the Cancer Institute at Tongji University, discusses findings from the phase 3 HARMONi-2 trial (NCT05499390) evaluating ivonescimab (AK112) vs pembrolizumab as first-line treatment for patients with PD-L1–positive advanced non–small cell lung cancer (NSCLC).

This randomized, open-label study enrolled patients with previously untreated advanced NSCLC who had a PD-L1 tumor proportion score of at least 1%. Findings demonstrated that ivonescimab produced a statistically significant improvement in progression-free survival (PFS) compared with pembrolizumab, Zhou begins. The median PFS was 11.14 months (95% CI, 7.33-not estimable) in the ivonescimab arm (n = 198) vs 5.82 months (95% CI, 5.03-8.21) in the pembrolizumab arm (n = 200; stratified HR, 0.51; 95% CI, 0.38-0.69; P < .0001). The 9-month PFS rates were 56% (95% CI, 47%-64%) in the ivonescimab group compared with 40% in the pembrolizumab group.

Additionally, ivonescimab generated an overall response rate of 50.0% (95% CI, 42.8%-57.2%) vs 38.5% (95% CI, 31.7-45.6) for pembrolizumab. The disease control rate was also improved at 89.9% (95% CI, 84.8%-93.7%) in the ivonescimab arm vs. 70.5% (95% CI, 63.7%-76.7%) in the pembrolizumab arm. Median duration of response was not reached in either treatment arm.

In terms of safety, ivonescimab demonstrated a manageable safety profile consistent with previous studies. Treatment-related adverse effects (TRAEs) of any grade were reported in 89.8% of patients in the ivonescimab arm vs. 81.9% in the pembrolizumab arm. Grade 3 or higher TRAEs occurred in 29.4% and 15.6% of patients, respectively. Serious TRAEs were observed in 20.8% of patients receiving ivonescimab and 16.1% of those receiving pembrolizumab. Discontinuation rates due to TRAEs were 1.5% and 3.0%, respectively. Treatment-related mortality was reported in 0.5% of patients receiving ivonescimab and 1.0% of those receiving pembrolizumab.

Notably, the incidence of high-grade bleeding effects remained low in patients with squamous cell carcinoma, despite the anti-VEGF activity of ivonescimab, Zhou states. The safety profile was comparable between treatment arms, and ivonescimab did not introduce new toxicity concerns, he adds.

These findings support further exploration of ivonescimab as a first-line standard-of-care option for patients with PD-L1–positive advanced NSCLC, Zhou concludes.