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 Zadeh; Tim F. Cloughesy; Minesh P. Mehta; Steven Piantadosi; Michael Weller; Amy B. Heimberger; Mustafa Khasraw

doi:10.1158/1078-0432.CCR-21-2681

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

Research output: Contribution to journal › Review article › peer-review

17 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 language	English (US)
Pages (from-to)	585-593
Number of pages	9
Journal	Clinical Cancer Research
Volume	28
Issue number	4
DOIs	https://doi.org/10.1158/1078-0432.CCR-21-2681
State	Published - Feb 15 2022

ASJC Scopus subject areas

Oncology
Cancer Research

MD Anderson CCSG core facilities

Biostatistics Resource Group

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10.1158/1078-0432.CCR-21-2681

Cite this

Singh, K., Batich, K. A., Wen, P. Y., Tan, A. C., Bagley, S. J., Lim, M., Platten, M., Colman, H., Ashley, D. M., Chang, S. M., Rahman, R., Galanis, E., Mansouri, A., Puduvalli, V. K., Reardon, D. A., Sahebjam, S., Sampson, J. H., Simes, J., Berry, D. A., ... Khasraw, M. (2022). Designing Clinical Trials for Combination Immunotherapy: A Framework for Glioblastoma. Clinical Cancer Research, 28(4), 585-593. https://doi.org/10.1158/1078-0432.CCR-21-2681

Singh, K, Batich, KA, Wen, PY, Tan, AC, Bagley, SJ, Lim, M, Platten, M, Colman, H, Ashley, DM, Chang, SM, Rahman, R, Galanis, E, Mansouri, A, Puduvalli, VK, Reardon, DA, Sahebjam, S, Sampson, JH, Simes, J, Berry, DA, Zadeh, G, Cloughesy, TF, Mehta, MP, Piantadosi, S, Weller, M, Heimberger, AB & Khasraw, M 2022, 'Designing Clinical Trials for Combination Immunotherapy: A Framework for Glioblastoma', Clinical Cancer Research, vol. 28, no. 4, pp. 585-593. https://doi.org/10.1158/1078-0432.CCR-21-2681

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title = "Designing Clinical Trials for Combination Immunotherapy: A Framework for Glioblastoma",

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.",

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

note = "Publisher Copyright: {\textcopyright} 2021 The Authors; Published by the American Association for Cancer Research",

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AU - Bagley, Stephen J.

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AU - Ashley, David M.

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AU - Rahman, Rifaquat

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AU - Puduvalli, Vinay K.

AU - Reardon, David A.

AU - Sahebjam, Solmaz

AU - Sampson, John H.

AU - Simes, John

AU - Berry, Donald A.

AU - Zadeh, Gelareh

AU - Cloughesy, Tim F.

AU - Mehta, Minesh P.

AU - Piantadosi, Steven

AU - Weller, Michael

AU - Heimberger, Amy B.

AU - Khasraw, Mustafa

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AB - 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.

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Designing Clinical Trials for Combination Immunotherapy: A Framework for Glioblastoma

Abstract

ASJC Scopus subject areas

MD Anderson CCSG core facilities

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