Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:

Lung cancer

The evolving immuno-angiogenic paradigm in NSCLC: lessons from ivonescimab

Nature Reviews Clinical Oncology volume 22, pages 461–462 (2025)Cite this article

Subjects

The HARMONi-2 trial demonstrated a significant improvement in progression-free survival with ivonescimab, a bispecific PD-1×VEGF antibody, versus pembrolizumab in patients with PD-L1-positive advanced-stage non-small-cell lung cancer. Ivonescimab might enhance antitumour immunity by normalizing the tumour vasculature and reversing immunosuppression. Although promising, global applicability of ivonescimab awaits further validation, including overall survival results, in diverse populations.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Learn more

Prices may be subject to local taxes which are calculated during checkout

References

  1. Xiong, A. et al. Ivonescimab versus pembrolizumab for PD-L1-positive non-small cell lung cancer (HARMONi-2): a randomised, double-blind, phase 3 study in China. Lancet 405, 839–849 (2025).

    Article  CAS  PubMed  Google Scholar 

  2. Kim, T. K., Vandsemb, E. N., Herbst, R. S. & Chen, L. Adaptive immune resistance at the tumour site: mechanisms and therapeutic opportunities. Nat. Rev. Drug Discov. 21, 529–540 (2022).

    Article  CAS  PubMed  Google Scholar 

  3. Pérez-Gutiérrez, L. & Ferrara, N. Biology and therapeutic targeting of vascular endothelial growth factor A. Nat. Rev. Mol. Cell Biol. 24, 816–834 (2023).

    Article  PubMed  Google Scholar 

  4. Sun, Y. et al. Blockade of the CD93 pathway normalizes tumor vasculature to facilitate drug delivery and immunotherapy. Sci. Transl. Med. 13, eabc8922 (2021).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Rini, B. I. et al. Pembrolizumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N. Engl. J. Med. 380, 1116–1127 (2019).

    Article  CAS  PubMed  Google Scholar 

  6. Finn, R. S. et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N. Engl. J. Med. 382, 1894–1905 (2020).

    Article  CAS  PubMed  Google Scholar 

  7. Socinski, M. A. et al. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC. N. Engl. J. Med. 378, 2288–2301 (2018).

    Article  CAS  PubMed  Google Scholar 

  8. Herbst, R. S. et al. Lenvatinib plus pembrolizumab, pemetrexed, and a platinum (len + pembro + chemo) as first-line therapy for metastatic non squamous non-small cell lung cancer (NSCLC): phase III LEAP-006. Immuno-Oncol. Technol. 20, 100536 (2023).

    Article  Google Scholar 

  9. Reckamp, K. L. et al. Phase II randomized study of ramucirumab and pembrolizumab versus standard of care in advanced non-small-cell lung cancer previously treated with immunotherapy-Lung-MAP S1800A. J. Clin. Oncol. 40, 2295–2306 (2022).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wang, M., Herbst, R. S. & Boshoff, C. Toward personalized treatment approaches for non-small-cell lung cancer. Nat. Med. 27, 1345–1356 (2021).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank A. Blevins Pifer and A. Incassati for their editorial input. The work of L.C. has been supported by the UTC Chair at Yale, the Yale Cancer Center and the NIH (grant P50 CA196530). The work of R.S.H. has been supported by Yale Cancer Center and the NIH (2P50CA196530).

Author information

Authors and Affiliations

  1. Yale Cancer Center, Section of Medical Oncology and Hematology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT, USA

    Roy S. Herbst & Lieping Chen

  2. Department of Immunobiology, Yale University School of Medicine, New Haven, CT, USA

    Lieping Chen

Authors
  1. Roy S. Herbst
    View author publications

    Search author on:PubMed Google Scholar

  2. Lieping Chen
    View author publications

    Search author on:PubMed Google Scholar

Corresponding author

Correspondence to Roy S. Herbst.

Ethics declarations

Competing interests

R.S.H. has received consulting fees from AbbVie, AstraZeneca, Bolt Biotherapeutics, Bristol Myers Squibb, Candel Therapeutics, Checkpoint Therapeutics, Cybrexa Therapeutics, DynamiCure, Eli Lilly and Company, EMD Serono, Genentech, Gilead, I-Mab, Immunocore, Janssen, Merck, NextCure, Normunity, Novartis, Pfizer, Regeneron Pharmaceuticals, Roche, Sanofi, and Seattle Genetics; and research funding from AstraZeneca, Eli Lilly and Company, Genentech/Roche and Merck. R.S.H. is on the Board of Directors of Immunocore. L.C. has received research funding from Normunity; and has been a scientific founder/board member/observer and/or advisor for Chia Tai Tian Qing Pharm, DynamiCure, NextCure, Normunity, OncoC4, Tcelltech, and Zai Lab in the past 12 months.

Additional information

Related links

Pragmatica-Lung: https://www.cancer.gov/types/lung/research/pragmatica-lung-cancer-trial

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Herbst, R.S., Chen, L. The evolving immuno-angiogenic paradigm in NSCLC: lessons from ivonescimab. Nat Rev Clin Oncol 22, 461–462 (2025). https://doi.org/10.1038/s41571-025-01024-y

Download citation

  • Published:

  • Version of record:

  • Issue date:

  • DOI: https://doi.org/10.1038/s41571-025-01024-y

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing