Research in Context

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Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy in first-line advanced squamous NSCLC

In this study, generalisability not yet established, with a global phase 3 underway to assess it, the authors reported that first-line ivonescimab plus chemotherapy significantly improved overall survival versus tislelizumab plus chemotherapy, with a manageable safety profile.

  • Shun Lu, MD; Baogang Liu, MD; Yongzhong Luo, MD; Longhua Sun, MD; Lin Wu, MD; Zhengxiang Han, MD; et al.

  • May 31, 2026

  • The Lancet
  • Volume 407, Issue 10548, Pages 2620–2629
  • 10.1016/S0140-6736(26)00966-9

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Evidence before this study

We searched PubMed April 27, 2026, for articles published between Jan 1, 2016, and April 23, 2026, using the terms “PD-1 OR PD-L1 OR CTLA-4 OR VEGF AND metastatic AND first line OR previously untreated AND squamous AND non-small-cell lung cancer OR NSCLC”, and applied clinical trial as a filter, yielding 49 results. Several randomised phase 3 studies have compared the efficacy of anti-programmed death-ligand 1 (PD-L1) and programmed death 1 (PD-1) agents plus chemotherapy versus chemotherapy alone as first-line therapy in advanced squamous non-small-cell lung cancer (NSCLC), and demonstrated the added value of anti-PD-L1 or anti-PD-1 agents plus chemotherapy. The combination of anti-PD-1 plus chemotherapy has become the standard of care. However, among key phase 3 studies, only KEYNOTE-407 reported that pembrolizumab plus chemotherapy significantly improved both progression-free survival and overall survival compared with chemotherapy alone. In the IMPOWER 131 study, atezolizumab plus chemotherapy significantly prolonged progression-free survival but failed to show an overall survival benefit. In the ASTRUM-004 study, where overall survival was a statistically powered secondary endpoint, serplulimab plus chemotherapy significantly extended median overall survival compared with chemotherapy. For most other immunotherapy plus chemotherapy combinations, the study design was not powered to establish statistically significant overall survival superiority. Therefore, further studies are warranted to validate the efficacy of novel therapeutic agents for patients with squamous NSCLC.

Added value of this study

To our knowledge, this is the first study showing that adding anti-angiogenic blockade to anti-PD-1 plus chemotherapy achieves superior overall survival benefits compared with anti-PD-1 plus chemotherapy in patients with advanced squamous NSCLC, facilitated by a PD-1–VEGF bispecific antibody. This study enables safe delivery of anti-angiogenic therapy in patients with squamous NSCLC, while demonstrating significant improvements in both progression-free survival and overall survival. The incidence of grade 3 or higher haemorrhage remained 3%. Immune-related adverse events of grade 3 and higher were comparable between the two groups.

Implications of all the available evidence

As first-line treatment in patients with advanced squamous NSCLC, ivonescimab plus chemotherapy significantly improved overall survival compared with tislelizumab plus chemotherapy, with a manageable safety profile. This regimen could provide a novel treatment option for those patients. A global phase 3 study is underway to determine the generalisability of these findings.

Source: The Lancet

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