New immunotherapeutic drugs in advanced non-small cell lung cancer (NSCLC): from preclinical to phase I clinical trials

Danilo Rocco, Vanesa Gregorc, Luigi Della Gravara, Chiara Lazzari, Giovanni Palazzolo, Cesare Gridelli

Research output: Contribution to journalReview articlepeer-review


Introduction: 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. Areas covered: 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 Expert opinion: 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.

Original languageEnglish
JournalExpert Opinion on Investigational Drugs
Publication statusPublished - 2020


  • CAR T
  • GITR
  • IDO
  • immune checkpoint inhibitors
  • immune modulators
  • LAG3
  • Non-small cell lung cancer
  • OX40
  • TIM-3

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)


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