Ivonescimab plus chemo confers progression-free survival advantage in pretreated NSCLC

Ivonescimab plus chemotherapy has a tolerable safety profile and appears to significantly prolong progression-free survival (PFS) in patients with nonsmall cell lung cancer (NSCLC) whose disease progressed while receiving EGFR tyrosine kinase inhibitor (EGFR-TKI) therapy, according to interim data from the phase III HARMONi-A study.

A total of 322 patients were randomly assigned to receive either ivonescimab (n=161, median age 59.6 years, 52.2 percent female) or placebo (n=161, median age 59.4 years, 50.9 percent female) in addition to pemetrexed and carboplatin once every 3 weeks for 4 cycles, followed by maintenance therapy with ivonescimab plus pemetrexed or placebo plus pemetrexed.

The primary endpoint of PFS, assessed by an independent radiographic review committee (IRRC) per Response Evaluation Criteria in Solid Tumors version 1.1, was evaluated in the intention-to-treat population. The results of the first planned interim analysis are reported.

Over a median follow-up time of 7.89 months, the median PFS was longer by 2.3 months in the ivonescimab arm than in the placebo arm (7.1 months, 95 percent confidence interval [CI], 5.9–8.7 vs 4.8 months, 95 percent CI, 4.2–5.6; hazard ratio [HR], 0.46, 95 percent CI, 0.34–0.62; p<0.001).

The PFS benefit with ivonescimab was observed across almost all subgroups, including patients whose disease progressed while receiving third-generation EGFR-TKI therapy (HR, 0.48, 95 percent CI, 0.35–0.66) and those with brain metastases (HR, 0.40, 95 percent CI, 0.22–0.73).

The objective response rate was 50.6 percent (95 percent CI, 42.6–58.6) in the ivonescimab arm and 35.4 percent (95 percent CI, 28.0–43.3) in the placebo arm (difference, 15.6 percent, 95 percent CI, 5.3–26.0; p=0.006). The median overall survival data have yet to reach maturity, with 69 deaths recorded at data cutoff.

In terms of safety, grade 3 or higher treatment-emergent adverse events (TEAEs) were documented in 99 patients (61.5 percent) in the ivonescimab arm and in 79 patients (49.1 percent) in the placebo arm. The most frequent TEAEs were chemotherapy-related.

Grade 3 or higher immune-related AEs were reported in 10 patients (6.2 percent) in the ivonescimab arm and in four (2.5 percent) in the placebo arm. Grade 3 or higher vascular endothelial growth factor–related adverse events occurred in five (3.1 percent) and four (2.5 percent) patients in the respective arms.