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Translational Biomarkers: Application in the Clinical Development of Combination Therapies

  • Selvakumar Sukumar
  • Niña G. Caculitan
Chapter

Abstract

Development of appropriate pharmacodynamic and safety markers early in drug development can result in a higher probability of success for new drug candidates. As the overarching goal of cancer therapy is to effectively eradicate cancer in a manner that is tolerable and safe for use in the intended patient population, application of biomarkers can facilitate effective patient selection with a positive impact on the final therapeutic outcome. Additionally, combination therapies for the treatment of cancer have emerged as an effective way to anticipate and overcome cancer heterogeneity and resistance. With the emergence of cancer immune oncology (IO), clinical trials for the combination of traditional oncology drugs and immune checkpoint blockade are ongoing. The discussions in this chapter are focused on the use of current and emergent biomarkers in the design and development of treatment combinations for cancer, with a special emphasis on emerging IO therapies.

Abbreviations

BIO

Biotechnology innovation orgaization

CAP

College of American Pathologists

CLIA

Clinical Laboratory Improvement Amendments

CO

Companion diagnostics

FDA

Food and Drug Administration

FFPE

Formalin fixed paraformaldehyde embedded

FIH

First-in-human dose

GEP

Gene expression profile

GLP

Good laboratory practice

H&E

Hematoxylin and eosin

HED

Human equivalent dose

HLA

Human leukocyte antigen

IHC

Immunohistochemistry test

IO

Immuno-oncology

irAEs

Immune-related adverse events

MABEL

Minimally anticipated biological effect level

MHC

Major histocompatibility complex

MMR

DNA mismatch repair

MoA

Mechanism of action

NHP

Nonhuman primates

NOAEL

No observed adverse effect level

NSCLC

Non-small cell lung cancer

PBMC

Peripheral blood mononuclear cells

PD

Pharmacodynamic

PFS

Progression-free survival

PoC

Proof of concept

PoM

Proof of mechanism

RO

Receptor occupancy

TCR

T-cell receptor

TPS

Tumor proportion score

TRAE

Treatment-related adverse events

VEGF

Vascular endothelial growth factor

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Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  • Selvakumar Sukumar
    • 1
  • Niña G. Caculitan
    • 2
  1. 1.CSL BehringKing of PrussiaUSA
  2. 2.Gritstone OncologyEmeryvilleUSA

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