In the phase 3 HARMONi-6 trial, the bispecific antibody ivonescimab (targeting both PD-1 and VEGF) plus carboplatin/paclitaxel significantly improved progression-free survival (PFS) compared with the PD-1 inhibitor tislelizumab plus the same chemotherapy backbone as first-line treatment for advanced squamous non–small cell lung cancer (NSCLC). Median PFS was 11.1 vs 6.9 months (HR = 0.60), with benefit seen across PD-L1 subgroups and higher objective response rates (75.9% vs 66.5%) and longer median duration of response (11.2 vs 8.4 months) in the ivonescimab arm. Grade ≥3 treatment-related adverse events (AEs) were somewhat more frequent with ivonescimab (63.9% vs 54.3%), though high-grade immune-related AEs were similar between arms.
Dr. Myung Ju Ahn called HARMONi-6 an important advance in squamous NSCLC, a setting where options remain limited and bevacizumab-like anti-VEGF strategies have historically been constrained by bleeding risk. Ivonescimab builds on earlier HARMONi-2 data showing improved PFS vs pembrolizumab with low rates of classic anti-VEGF toxicities, and its HARMONi-6 results compare favorably to benchmarks such as KEYNOTE-407. However, Dr. Ahn emphasized that overall survival data are still immature, several patients on ivonescimab experienced serious hemorrhage (mostly with preexisting high-risk features), and the trial was conducted exclusively in China. She stressed that confirmation in broader populations, careful patient selection—especially for those with central tumors or prior hemoptysis—and results from the ongoing global phase 3 HARMONi-3 trial will be critical to determine whether ivonescimab plus chemotherapy should be widely adopted as a new standard.
Reference: Helwick C. Ivonescimab, a Dual-Targeting Bispecific Antibody, Improves Progression-Free Survival in Squamous NSCLC. The ASCO Post. Published December 10, 2025. Accessed December 1, 2025. https://ascopost.com/issues/december-10-2025-supplement-conference-highlights-esmo-2025/ivonescimab-a-dual-targeting-bispecific-antibody-improves-progression-free-survival-in-squamous-nsclc/
