A phase I/II clinical trial on the efficacy and safety of NKT cells combined with gefitinib for advanced EGFR-mutated non-small-cell lung cancer

BMC Cancer

Junrong Li¹  Wanjun Yu²  Yali Ma²  Sheng Xia²  Chaoming Mao³  Yuepeng Zhou⁴  Deqiang Wang⁴  Chunhua Dai⁴  Xiujuan Fan⁴  Xiaoqin Li⁴  Deyu Chen⁴  Fei Ye⁴  Xiao Yuan⁴  Jian Li⁵  Fenhong Qian⁵  Zhenhong Guo⁶  Minghui Zhang⁷  Huazhang An⁸ 

[1] Department of Epidemiology and Biostatistics, School of Medicine, Jiangsu University, Zhenjiang, China;Department of Immunology, School of Medicine, Jiangsu University, Zhenjiang, China;Department of Nuclear Medicine, The Affiliated Hospital of Jiangsu University, Zhenjiang, China;Department of Oncology, The Affiliated Hospital of Jiangsu University, Zhenjiang, China;Department of Respiratory, The Affiliated Hospital of Jiangsu University, Zhenjiang, China;National Key Laboratory of Medical Immunology & Institute of Immunology, Second Military Medical University, Shanghai, China;School of Medicine, Tsinghua University, Beijing, China;Shandong Provincial Qianfoshan Hospital, Shandong First Medical University, Jinan, Shandong, China;

关键词: Non-small-cell lung cancer;    Natural killer T cell;    Immunotherapy;    Gefitinib;    Randomized controlled trial;   

DOI  :  10.1186/s12885-021-08590-1

来源: Springer

【 摘 要 】

BackgroundEpidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, have achieved good efficacy in EGFR mutation-positive non-small-cell lung cancer (NSCLC) patients, but eventual drug resistance is inevitable. Thus, new TKI-based combination therapies should be urgently explored to extend the overall survival time of these patients. CD8 + CD56+ natural killer T (NKT) cells are a natural and unique subset of lymphocytes in humans that present characteristics of T and NK cells and exert cytotoxicity on tumour cells in a granzyme B-dependent manner. The aim of this trial was to explore the efficacy and safety of CD8 + CD56+ NKT cell immunotherapy combined with gefitinib in patients with advanced EGFR-mutated NSCLC.MethodsThe study was designed as a prospective, randomized, controlled, open-label, phase I/II trial that includes 30 patients with EGFR mutation-positive stage III/IV NSCLC. All patients will be randomized in blocks at a 1:1 ratio and treated with gefitinib 250 mg/day monotherapy or combination therapy with allogeneic CD8 + CD56+ NKT cell infusions twice per month for 12 cycles or until disease progression occurs. The effectiveness of this treatment will be evaluated based on by progression-free survival (PFS), the time to progression (TTP), overall response rate (ORR), disease control rate (DCR) and overall survival (OS). The safety of the trail is being assessed based on adverse events (AEs). Recruitment and data collection, which started in December 2017, are ongoing.DiscussionAlthough immunotherapy, including programmed death-1/programmed death-1 ligand (PD-1/PD-L1) immunotherapy, has been used for NSCLC treatment with or without EGFR-TKIs, its clear efficacy still has not been shown. Assessing the safety and therapeutic potential of allogeneic CD8 + CD56+ NKT killer cells in combination with EGFR-TKIs in NSCLC will be of great interest.Trial registrationThis trial (Phase I/II Trails of NKT Cell in Combination With Gefitinib For Non Small Cell Lung Cancer) was registered on 21 November 2017 with www.chictr.org.cn, ChiCTR-IIR-17013471.

【 授权许可】

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