Ivonescimab Extends Survival in Advanced Squamous Non-Small Cell Lung Cancer

Patients with previously untreated advanced squamous non-small cell lung cancer (NSCLC) lived longer when treated with ivonescimab plus chemotherapy compared with tislelizumab plus chemotherapy, according to findings from the phase 3 HARMONI-6 trial presented at the 2026 ASCO Annual Meeting.

The study was presented by Dr. Shun Lu, and evaluated ivonescimab, a bispecific antibody designed to target both PD-1 and VEGF. Investigators reported that the regimen improved overall survival while maintaining a manageable safety profile in the first-line treatment setting.

Main Data That Support the Findings

The trial met its key overall survival endpoint. Overall survival measures the length of time patients live after starting treatment, regardless of what happens to their cancer. Patients who received ivonescimab plus chemotherapy achieved a median overall survival of 27.89 months compared with 23.69 months for those treated with tislelizumab plus chemotherapy.

Researchers reported that patients treated with ivonescimab experienced a 34% lower risk of death than those who received the comparator regimen.

At 12 months, 78.9% of patients in the ivonescimab arm were alive compared with 72.2% of patients in the tislelizumab arm. At 24 months, those rates were 64.7% and 48.6%, respectively.

The survival benefit appeared consistent across several patient subgroups, including those grouped by age, sex and ECOG performance status. Benefits were also observed regardless of PD-L1 expression level. Among patients whose tumors had PD-L1 expression below 1%, treatment with ivonescimab was associated with a 36% lower risk of death compared with tislelizumab. Among those with PD-L1 expression of 1% or higher, ivonescimab was associated with a 32% lower risk of death.

These findings build on a previous analysis that met the study’s primary endpoint of progression-free survival, which measures how long patients live without their cancer growing or spreading. In that earlier analysis, patients receiving ivonescimab lived a median of 11.1 months without their cancer growing or spreading compared with 6.9 months for those receiving tislelizumab. Ivonescimab was associated with a 40% lower risk of disease progression or death.

“HARMONI-6 support[s] adoption of ivonescimab with chemotherapy as a new standard [of care] for patients with advanced squamous non-small cell lung cancer receiving first-line treatment in China,” Lu said during his presentation.

Trial Details of HARMONI-6

HARMONI-6 is a multicenter, randomized, double-blind phase 3 study conducted in China.

The trial enrolled 532 patients with stage IIIB to IV squamous NSCLC who had not previously received systemic treatment for advanced disease and whose tumors did not harbor EGFR or ALK alterations.

Patients were randomly assigned to receive either ivonescimab plus carboplatin and paclitaxel or tislelizumab plus carboplatin and paclitaxel. Chemotherapy was given for up to four cycles, followed by maintenance treatment with the assigned immunotherapy-based regimen for up to 24 months.

The study population was balanced between treatment groups. More than 90% of patients had stage IV disease, and approximately 39.5% of patients in each treatment arm had PD-L1 expression below 1%.

Among the 266 patients assigned to ivonescimab, 182 had discontinued treatment at the time of data cutoff, most commonly because their disease progressed on imaging scans. In the tislelizumab arm, 186 of 266 patients had discontinued treatment, with disease progression also representing the most common reason.

Subsequent anticancer therapy was administered to 35.7% of patients in the ivonescimab group and 36.5% of those in the tislelizumab group.

Safety of Ivonescimab Plus Chemotherapy

Investigators reported that ivonescimab plus chemotherapy had a manageable safety profile that was generally consistent with previous studies.

Treatment-related side effects of grade 3 or higher occurred in 69.2% of patients who received ivonescimab and 58.9% of patients who received tislelizumab. Serious treatment-related side effects were reported in 41.4% and 34.3% of patients, respectively.

The most common treatment-related side effects included hair loss, anemia and decreased neutrophil counts, a type of white blood cell that helps the body fight infection.

Because ivonescimab targets VEGF, researchers closely monitored VEGF-related side effects. Proteinuria, or protein in the urine, hemorrhage and hypertension occurred more frequently among patients receiving ivonescimab. Most of these events were low grade, although some patients experienced grade 3 or higher proteinuria or hypertension.

Treatment discontinuations caused by treatment-related side effects occurred in 5.3% of patients in the ivonescimab arm and 4.5% of patients in the tislelizumab arm. Treatment-related deaths occurred in 3.8% and 4.2% of patients, respectively.

Investigators noted that the study population consisted exclusively of patients treated in China. A global phase 3 trial, HARMONI-3, is ongoing to further evaluate the regimen in a broader patient population.

Reference

1. “Ivonescimab Plus Chemotherapy Versus Tislelizumab Plus Chemotherapy in Previously Untreated Advanced Squamous Non-Small Cell Lung Cancer: Overall Survival Results of the Phase 3 HARMONI-6” by Dr. Shun Lu, et al., presented at the 2026 ASCO Annual Meeting.

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