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Anti-PD1 based precision induction therapy in unresectable stage III non-small cell lung cancer: a phase II umbrella clinical trial

Author

Listed:
  • Chengxiang Yi

    (Tongji University)

  • Dongliang Bian

    (Tongji University)

  • Jue Wang

    (Tongji University)

  • Shiqi Hu

    (The First Affiliated Hospital of Wenzhou Medical University)

  • Liangdong Sun

    (Tongji University)

  • Yilv Yan

    (Tongji University)

  • Suyu Wang

    (Tongji University)

  • Ziyun Shen

    (Tongji University)

  • Huansha Yu

    (Tongji University)

  • Yong Yang

    (Tongji University)

  • Yirui Zhou

    (Tongji University)

  • Xiaogang Liu

    (Tongji University)

  • Nan Song

    (Tongji University)

  • Yuming Zhu

    (Tongji University)

  • Deping Zhao

    (Tongji University)

  • Gening Jiang

    (Tongji University)

  • Liang Duan

    (Tongji University)

  • Wenxin He

    (Tongji University)

  • Dong Xie

    (Tongji University)

  • Jie Dai

    (Tongji University)

  • Lele Zhang

    (Tongji University)

  • Peng Zhang

    (Tongji University
    The First Affiliated Hospital of Wenzhou Medical University)

Abstract

The efficacy and safety of induction-immunotherapy followed by surgery for unresectable Stage III non-small cell lung cancer (NSCLC) remain challenging. In this open-label, single-center, phase II clinical umbrella trial (ChiCTR2000035367), 100 unresectable Stage III NSCLC patients are enrolled. Patients with PD-L1 expression ≥ 50% but contraindications to anti-angiogenic therapy receive immuno-monotherapy. Patients with PD-L1 expression ≥ 1% and no contraindications to anti-angiogenic therapy receive immunotherapy plus anti-angiogenesis therapy. Patients with PD-L1 expression between 1% and 49%, contraindications to anti-angiogenic therapy, or negative/unknown PD-L1 expression receive chemoimmunotherapy. The primary endpoint is the major pathological response (MPR) rate. Among 47 surgically-treated patients, the MPR rate is 61.7% (95% confidence interval [CI]: 46.4%-75.5%), achieving the prespecified endpoint. For secondary endpoints, the objective response rate for all patients is 54.0% (95% CI: 43.7-64.0). The median event-free survival is 29.9 months (95% CI: 17.0-42.7). Most common adverse event is anemia (49.0%). Exploratory transcriptomic analyses reveal Bone Marrow Stromal Cell Antigen 1 (BST1) as a promising biomarker for response to chemoimmunotherapy. Generally, for unresectable stage III NSCLC patients, anti-PD1 based induction-therapy according to PD-L1 expression and contraindication to antiangiogenic therapy followed by surgery is a feasible option.

Suggested Citation

  • Chengxiang Yi & Dongliang Bian & Jue Wang & Shiqi Hu & Liangdong Sun & Yilv Yan & Suyu Wang & Ziyun Shen & Huansha Yu & Yong Yang & Yirui Zhou & Xiaogang Liu & Nan Song & Yuming Zhu & Deping Zhao & Ge, 2025. "Anti-PD1 based precision induction therapy in unresectable stage III non-small cell lung cancer: a phase II umbrella clinical trial," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57184-z
    DOI: 10.1038/s41467-025-57184-z
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    References listed on IDEAS

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    1. Kosuke Yoshihara & Maria Shahmoradgoli & Emmanuel Martínez & Rahulsimham Vegesna & Hoon Kim & Wandaliz Torres-Garcia & Victor Treviño & Hui Shen & Peter W. Laird & Douglas A. Levine & Scott L. Carter , 2013. "Inferring tumour purity and stromal and immune cell admixture from expression data," Nature Communications, Nature, vol. 4(1), pages 1-11, December.
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