Ivonescimab Plus Chemotherapy May Be New Standard of Care for Squamous Non-Small Cell Lung Cancer
A new treatment combination of ivonescimab plus chemotherapy is showing significant promise as a first-line therapy for advanced or metastatic squamous non-small cell lung cancer (NSCLC), according to findings presented at the European Society for Medical Oncology (ESMO) Congress 2025. The results from the phase 3 HARMONi-6 trial suggest this regimen “may be a new standard of care” for this challenging cancer type.
Understanding the HARMONi-6 Trial
The HARMONi-6 trial, conducted at 50 sites across China, involved 532 patients with previously untreated stage IIIB-IV squamous NSCLC. Patients were randomly assigned to receive either ivonescimab (20 mg/kg) or tislelizumab (200 mg) every three weeks, in combination with paclitaxel (175 mg/m2) and carboplatin (AUC 5) for four cycles. Following the initial cycles, patients received maintenance treatment with either ivonescimab or tislelizumab monotherapy for up to 24 months.
Randomization was stratified based on disease stage (IIIB/IIIC versus IV) and PD-L1 tumor proportion score (≥1% vs <1%). The primary endpoint of the study was progression-free survival (PFS), assessed by an independent radiographic review committee using RECIST v1.1 criteria. Overall survival is a key secondary endpoint.
Patient Characteristics
The study population included patients aged 18-75 years with a good performance status (Eastern Cooperative Oncology Group score of 0 or 1). Approximately two-thirds of patients (63.2%) had central tumors, 8.8% had tumor cavitation and 17.5% had major blood vessel encasement.
Key Findings and Implications
The HARMONi-6 trial demonstrated a significant improvement in progression-free survival with the ivonescimab combination. Previous research had already shown ivonescimab improved PFS compared to pembrolizumab in patients with a PD-L1 tumor proportion score of 1% or higher. Notably, HARMONi-6 evaluated the ivonescimab combination regardless of PD-L1 expression levels, potentially broadening the applicability of this treatment approach.
Shun Lu, MD, PhD, chief of Shanghai Lung Cancer Center at the Shanghai Chest Hospital of Shanghai Jiao Tong University, presented these findings at the ESMO 2025 Presidential Symposium.
Looking Ahead
The results of the HARMONi-6 trial are encouraging and suggest that ivonescimab plus chemotherapy could become a new standard of care for patients with advanced squamous NSCLC. Further follow-up will be crucial to assess the impact of this combination on overall survival. Ongoing research will similarly help to identify which patients are most likely to benefit from this treatment approach.