Abstract
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.
Highlights
Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, have achieved good efficacy in epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) patients, but eventual drug resistance is inevitable
Different types of killer cells combined with surgery and chemoradiotherapy have been explored for immunotherapy in NSCLC, including tumour-infiltrating lymphocytes (TILs) and dendritic cell-cytokine induced killer (DC-CIK) cells [31,32,33]
We used allogeneic CD8 + CD56+ killer cells combined with gefitinib to treat NSCLC with EGFR mutations
Summary
Objectives The aim of this trial is to assess whether the proposed allogeneic NKT cell adoptive transfer, when given in combination with gefitinib, warrants further consideration based on its safety and efficacy for the treatment of advanced EGFR-mutant NSCLCs. This trial aims to include only patients with advanced NSCLC (III/IV) harbouring mutated EGFR (exon 19 deletion or exon 21 Leu858 Arg point mutation) who can be effectively treated with gefitinib. This is an exploratory study to test the safety and efficacy of the intravenous infusion of CD8 + CD56+ NKT cells, which replicates a planned larger study in at a smaller scale. The relationship between abnormal changes and cell preparation will be further analysed
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