Phase I/II Trial of Immunotherapy With Durvalumab and Tremelimumab With Continuous or Intermittent MEK Inhibitor Selumetinib in NSCLC: Early Trial Report

Pierre Olivier Gaudreau, J. Jack Lee, John V. Heymach, Don L. Gibbons

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Current strategies to improve clinical outcomes in v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog-mutant non–small-cell lung cancer (NSCLC) patients include mitogen-activated protein kinase kinase 1 inhibitor and programmed death (PD) 1 (PD-1)/PD ligand 1 (PD-L1) immune checkpoint blockade combinations. Experience from treatment of melanoma suggests that anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and anti-PD-1/PD-L1 combinations improve outcomes, but similar benefits remain to be seen for treatment of NSCLC. This report describes a single center, investigator-initiated phase I/II clinical trial to compare 2 combination schedules of intermittent or continuous selumetinib (AZD6244, ARRY-142886), tremelimumab (anti-CTLA-4), and durvalumab (anti-PD-L1) treatment with historical controls in patients with previously treated, unresectable NSCLC. Forty patients will be accrued at the University of Texas M.D. Anderson Cancer Center. Primary objectives include maximum tolerated dose (dose escalation phase) and progression-free survival (dose expansion phase). Secondary objectives include response rate according to Response Evaluation Criteria In Solid Tumors version 1.1, disease control rate, overall survival, safety, and duration of response. Exploratory objectives are to assess biomarkers of response and resistance on the basis of biopsies and peripheral blood taken before and after treatment using immune profiling, transcriptome, and protein readouts.

Original languageEnglish (US)
Pages (from-to)384-388
Number of pages5
JournalClinical Lung Cancer
Volume21
Issue number4
DOIs
StatePublished - Jul 2020

Keywords

  • Anti-CTLA-4
  • Anti-PD-L1
  • Non–small-cell lung cancer

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

MD Anderson CCSG core facilities

  • Biostatistics Resource Group

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