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. 2021 Jul 31;21(1):877. doi: 10.1186/s12885-021-08590-1.

Abstract

Background: Epidermal 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.

Methods: The 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.

Discussion: Although 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 registration: This 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 .

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

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II
  • Randomized Controlled Trial

MeSH terms

  • Adoptive Transfer* / adverse effects
  • Adoptive Transfer* / methods
  • B7-H1 Antigen / antagonists & inhibitors
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / etiology
  • Carcinoma, Non-Small-Cell Lung / therapy*
  • Combined Modality Therapy
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • Gefitinib / administration & dosage
  • Gefitinib / adverse effects
  • Gefitinib / therapeutic use*
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / etiology
  • Lung Neoplasms / therapy*
  • Molecular Targeted Therapy
  • Mutation*
  • Natural Killer T-Cells / immunology*
  • Natural Killer T-Cells / metabolism
  • Treatment Outcome

Substances

  • B7-H1 Antigen
  • CD274 protein, human
  • EGFR protein, human
  • ErbB Receptors
  • Gefitinib