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Sintilimab in combination with stereotactic body radiotherapy and granulocyte-macrophage colony-stimulating factor in metastatic non-small cell lung cancer: The multicenter SWORD phase 2 trial

Author

Listed:
  • Jianjiao Ni

    (Fudan University Shanghai Cancer Center
    Fudan University)

  • Xiaofei Wang

    (Duke University School of Medicine)

  • Lin Wu

    (Central South University)

  • Xinghao Ai

    (Shanghai Jiao Tong University)

  • Qian Chu

    (Huazhong University of Science and Technology)

  • Chengbo Han

    (Shengjing Hospital of China Medical University)

  • Xiaorong Dong

    (Huazhong University of Science and Technology)

  • Yue Zhou

    (Fudan University Shanghai Cancer Center
    Fudan University)

  • Yechun Pang

    (Fudan University Shanghai Cancer Center
    Fudan University)

  • Zhengfei Zhu

    (Fudan University Shanghai Cancer Center
    Fudan University
    Fudan University)

Abstract

This single-arm, multicenter, phase 2 trial (NCT04106180) investigated the triple combination of sintilimab (anti-PD1 antibody), stereotactic body radiotherapy (SBRT) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in metastatic non-small cell lung cancer (NSCLC). With a median follow-up of 32.1 months, 18 (36.7%, 90% CI 25.3%–49.5%) of the 49 evaluable patients had an objective response, meeting the primary endpoint. Secondary endpoints included out-of-field (abscopal) response rate (ASR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). The ASR was 30.6% (95% CI 18.3%–45.4%). The median PFS and OS were 5.9 (95% CI 2.5–9.3) and 18.4 (95% CI 9.7–27.1) months, respectively. Any grade and grade 3 TRAEs occurred in 44 (86.3%) and 6 (11.8%) patients, without grade 4–5 TRAEs. Moreover, in pre-specified biomarker analyses, SBRT-induced increase of follicular helper T cells (Tfh) in unirradiated tumor lesions and patient’s blood, as well as of circulating IL-21 levels, was found associated with improved prognosis. Taken together, the triple combination therapy was well tolerated with promising efficacy and Tfh may play a critical role in SBRT-triggered anti-tumor immunity in metastatic NSCLC.

Suggested Citation

  • Jianjiao Ni & Xiaofei Wang & Lin Wu & Xinghao Ai & Qian Chu & Chengbo Han & Xiaorong Dong & Yue Zhou & Yechun Pang & Zhengfei Zhu, 2024. "Sintilimab in combination with stereotactic body radiotherapy and granulocyte-macrophage colony-stimulating factor in metastatic non-small cell lung cancer: The multicenter SWORD phase 2 trial," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51807-7
    DOI: 10.1038/s41467-024-51807-7
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    References listed on IDEAS

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    2. Jae-Won Cho & Seyeon Park & Gamin Kim & Heonjong Han & Hyo Sup Shim & Sunhye Shin & Yong-Soo Bae & Seong Yong Park & Sang-Jun Ha & Insuk Lee & Hye Ryun Kim, 2021. "Dysregulation of TFH-B-TRM lymphocyte cooperation is associated with unfavorable anti-PD-1 responses in EGFR-mutant lung cancer," Nature Communications, Nature, vol. 12(1), pages 1-16, December.
    3. Gang Chen & Alexander C. Huang & Wei Zhang & Gao Zhang & Min Wu & Wei Xu & Zili Yu & Jiegang Yang & Beike Wang & Honghong Sun & Houfu Xia & Qiwen Man & Wenqun Zhong & Leonardo F. Antelo & Bin Wu & Xue, 2018. "Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response," Nature, Nature, vol. 560(7718), pages 382-386, August.
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