Department of Pulmonary Oncology, AORN Dei Colli Monaldi , Naples, Italy.
Department of Oncology, Division of Experimental Medicine, IRCCS San Raffaele , Milan, Italy.
Expert Opin Investig Drugs. 2020 Sep;29(9):1005-1023. doi: 10.1080/13543784.2020.1793956. Epub 2020 Jul 21.
The development of immune checkpoint inhibitors (ICI) has represented a revolution in the treatment of non-small cell lung cancer (NSCLC) and has established a new standard of care for different settings. However, through adaptive changes, cancer cells can develop resistance mechanisms to these drugs, hence the necessity for novel immunotherapeutic agents.
This paper explores the immunotherapeutics currently under investigation in phase I clinical trials for the treatment of NSCLC as monotherapies and combination therapies. It provides two comprehensive tables of phase I agents which are listed according to target, drug, drug class, mechanism of action, setting, trial identifier, and trial status. A comprehensive literature search was carried out to identify eligible studies from MEDLINE/PubMed and ClinicalTrials.gov.
A key hurdle to success in this field is our limited understanding of the synergic interactions of the immune targets in the context of the TME. While we can recognize the links between inhibitors and some particularly promising new targets such as TIM-3 and LAG3, we continue to develop approaches to exploit their interactions to enhance the immune response of the patient to tumor cells.
免疫检查点抑制剂（ICI）的发展代表了非小细胞肺癌（NSCLC）治疗领域的一场革命，为不同治疗环境确立了新的护理标准。然而，癌细胞可以通过适应性变化发展出对这些药物的耐药机制，因此需要新型免疫治疗药物。
本文探讨了目前正在进行的 I 期临床试验中用于治疗 NSCLC 的免疫疗法，包括单药治疗和联合治疗。它提供了两列 I 期药物的综合表，这些药物根据靶点、药物、药物类别、作用机制、治疗环境、试验标识符和试验状态进行了分类。通过对 MEDLINE/PubMed 和 ClinicalTrials.gov 进行全面的文献检索，确定了合格的研究。
在该领域取得成功的一个关键障碍是，我们对 TME 中免疫靶点的协同相互作用的了解有限。虽然我们可以认识到抑制剂与 TIM-3 和 LAG3 等一些特别有前途的新靶点之间的联系，但我们仍在继续开发利用它们相互作用的方法，以增强患者对肿瘤细胞的免疫反应。
