ESMO 2025 Bispecific antibody ivonescimab improves progression-free survival in advanced NSCLC

MedNet.nl: First-line treatment with ivonescimab in combination with chemotherapy significantly prolongs progression-free survival (PFS) in patients with advanced or metastatic non-small-cell lung cancer (NSCLC), compared with tislelizumab plus chemotherapy. This is shown by the phase 3 HARMONi-6 study.

Ivonescimab is a bispecific antibody targeting PD-1 and VEGF. The drug is registered in China for the treatment of NSCLC that has progressed after EGFR-TKI therapy and as first-line treatment for PD-L1-positive patients with advanced NSCLC. The HARMONi-6 study compared ivonescimab plus chemotherapy with the PD-1 inhibitor tislelizumab plus chemotherapy in previously untreated patients with advanced squamous cell NSCLC (stage IIIB–IV).

A total of 532 patients were randomized to receive ivonescimab or tislelizumab (both 3 cycles) in combination with chemotherapy, followed by maintenance treatment with ivonescimab and tislelizumab, respectively. The primary endpoint was independently assessed PFS.

PFS was significantly longer in the ivonescimab group, with a median PFS of 11.1 months versus 6.9 months in the tislelizumab group (HR=0.60). The combination with ivonescimab demonstrated a benefit in all subgroups studied. There was also a benefit in both patients with high and low PD-L1 expression. In addition, the number of patients with a response was significantly higher: 75.9% versus 66.5%. The median duration of response was 11.2 versus 8.4 months, respectively.

The toxicity profile was relatively similar. Serious treatment-related adverse events occurred in 32.3% and 30.2% of patients, respectively. And a respective 3.4% and 4.2% discontinued treatment due to side effects.

The researchers suggest that the combination with ivonescimab may represent a new standard first-line treatment for patients with advanced or metastatic squamous NSCLC.

Lu S, 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). ESMO 2025, abstract LBA4.

This article was originally published in Dutch on MedNet.nl