Ivonescimab/Chemo Improves Quality of Life in Frontline Squamous NSCLC

Updated results from the phase 3 HARMONi-6 trial (NCT05840016) demonstrated that patient-reported quality of life outcomes were improved with ivonescimab plus chemotherapy compared with tislelizumab-jsgr (Tevimbra) plus chemotherapy in the treatment of patients with first-line, advanced, squamous non–small cell lung cancer (NSCLC). These data were shared at the 2025 European Society for Medical Oncology (ESMO) Asia Congress.¹

Notably, the ivonescimab plus chemotherapy regimen offered better tolerability, enabled higher treatment adherence, and provided patients the ability to maintain better overall health status and quality of life over a longer period.

The time to deterioration in global health status/quality of life was meaningfully delayed in the ivonescimab arm compared with the tislelizumab arm (HR, 0.94). Additionally, the median progression-free survival (PFS) was 11.14 months in the ivonescimab arm vs 6.90 months in the tislelizumab arm (HR, 0.60; P <.0001). This benefit was consistent across all key subgroups.

Earlier in October 2025, results from HARMONi-6 were simultaneously presented at the ESMO 2025 Congress and published in The Lancet, showing that ivonescimab plus chemotherapy significantly improved progression-free survival (PFS) in this patient population.^2,3

The investigators noted that these results “further validate the breakthrough clinical value” of the ivonescimab plus chemotherapy regimen vs the tislelizumab combination, and that the experimental regimen addresses a critical clinical gap when anti-angiogenic agents, like bevacizumab (Avastin), display severe safety considerations when treating patients with squamous NSCLC.¹

The HARMONi-6 trial enrolled a total of 532 patients with well-balanced baseline characteristics, who were randomly assigned to receive either ivonescimab at 20 mg/kg every 3 weeks or tislelizumab at 200 mg every 3 weeks, with chemotherapy consisting of carboplatin and paclitaxel, followed by ivonescimab or tislelizumab on the same schedule for up to 24 months.

Eligible patients in the trial had pathologically confirmed squamous stage IIIB or IV NSCLC who had not received prior systemic therapy, had no EGFR mutations or ALK rearrangements, and had an ECOG performance status of 0 or 1.

Stage IV disease was noted in 92.3% of patients at enrollment, and central squamous histology in 63%; PD-L1 expression levels were aligned with clinical expectations.

Regarding safety, as presented in October 2025, with a data cutoff date of February 28, 2025, treatment-related adverse events (TRAEs) occurred in 99.2% of the ivonescimab group and 98.5% of the tislelizumab group, with grade 3 or higher TRAEs occurring in 63.9% and 54.3%, respectively. Serious TRAEs were reported in 32.3% and 30.2%, respectively, and TRAEs leading to treatment discontinuation and death were reported in 3.4% and 3.0% of the ivonescimab arm and 4.2% and 3.8% of the tislelizumab arm.

The most common TRAEs in the ivonescimab arm were alopecia (65.4%), anemia (53.0%), neutrophil count decreases (45.1%), and white blood cell count decreases (36.1%); the most common grade 3 or higher TRAEs were neutrophil count decreases (32.0%), white blood cell count decreases (10.9%), anemia (6.4%), and leukopenia (5.6%).

Any-grade immune-related AEs occurred in 27.4% and 25.3% of the ivonescimab and tislelizumab groups, respectively; grade 3 or higher events occurred in 9.0% and 10.2%. They led to ivonescimab or tislelizumab discontinuation in 1.1% and 2.3%, and death in 0% and 0.4%, respectively.

The investigators also noted possibly VEGF-related AEs. The most common in the ivonescimab arm were proteinuria (27.1%), hemorrhage (21.4%), and hypertension (10.2%); in the tislelizumab arm, they were the same but at rates of 10.9%, 9.4%, and 4.5%.

In July 2025, the supplemental new drug application for ivonescimab in combination with chemotherapy as first-line treatment for squamous NSCLC was accepted for review by the Center for Drug Evaluation of China’s National Medical Products Administration.

References

1. Significant improvement in quality of life reported in updated HARMONi-6 data for ivonescimab at ESMO Asia. News release. Akeso. December 8, 2025. Accessed December 9, 2025. https://tinyurl.com/2s4x7yk4
2. Lu S, Yang F, Jiang Z, et al. Phase III study of ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as first-line treatment for advanced squamous non-small cell lung cancer (HARMONi-6). Ann Oncol. 2025;36(suppl 2):S1728. doi:10.1016/j.annonc.2025.09.084
3. Chen Z, Yang F, Jiang Z, et al. Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (HARMONi-6): a randomised, double-blind, phase 3 trial. Lancet. 2025;406(10515):2078-2088. doi:10.1016/S0140-6736(25)01848-3