Designing Clinical Trials for Combination Immunotherapy: A Framework for Glioblastoma

Kirit Singh, Kristen A. Batich, Patrick Y. Wen, Aaron C. Tan, Stephen J. Bagley, Michael Lim, Michael Platten, Howard Colman, David M. Ashley, Susan M. Chang, Rifaquat Rahman, Evanthia Galanis, Alireza Mansouri, Vinay K. Puduvalli, David A. Reardon, Solmaz Sahebjam, John H. Sampson, John Simes, Donald A. Berry, Gelareh ZadehTim F. Cloughesy, Minesh P. Mehta, Steven Piantadosi, Michael Weller, Amy B. Heimberger, Mustafa Khasraw*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

2 Scopus citations

Abstract

Immunotherapy has revolutionized treatment for many hard-to-treat cancers but has yet to produce significant improvement in outcomes for patients with glioblastoma. This reflects the multiple and unique mechanisms of immune evasion and escape in this highly heterogeneous tumor. Glioblastoma engenders profound local and systemic immunosuppression and is remarkably effective at inducing T-cell dysfunction, posing a challenge to any immunotherapy-based approach. To overcome these mechanisms, multiple disparate modes of immune-oriented therapy will be required. However, designing trials that can evaluate these combinatorial approaches requires careful consideration. In this review, we explore the immunotherapy resistance mechanisms that have been encountered to date and how combinatorial approaches may address these. We also describe the unique aspects of trial design in both preclinical and clinical settings and consider endpoints and markers of response best suited for an intervention involving multiple agents.

Original languageEnglish (US)
Pages (from-to)585-593
Number of pages9
JournalClinical Cancer Research
Volume28
Issue number4
DOIs
StatePublished - Feb 15 2022

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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