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Combinations of Genomically and Immune-Targeted Therapies in Early-Phase Clinical Trials

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Early Phase Cancer Immunotherapy

Part of the book series: Current Cancer Research ((CUCR))

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Abstract

Advances in cancer treatment have evolved from relatively nonspecific application of cytotoxic agents to mechanism-based therapies targeting oncogenic signaling pathways and, more recently, to the development of immune-based therapies that seek to activate patients’ own immune system in order to reinitiate the antitumor immune response. Some genomically targeted therapies, in addition to inhibiting molecular pathways driving tumor growth and maintenance, also possess immune-modulatory effects such as increasing tumor immunogenicity, in part by increasing T-cell trafficking into the tumor stroma and enhancing expression of tumor antigens. These observations raise the intriguing possibility that some genomically targeted therapies may be effectively combined with immunotherapies to improve overall clinical outcomes. Here, we discuss the preclinical data that serve as the foundation for testing genomically targeted therapies with immune checkpoint inhibitors, such as monoclonal antibodies targeting cytotoxic T-lymphocyte associated antigen 4, programmed cell death protein 1, and PD-1 ligand 1, as well as the clinical status of key combination trials.

Funding: Funded in part by National Cancer Institute grant P30 CA016672 and the Joan and Irwin Jacobs Fund philanthropic fund.

Author’s Disclosures

Dr. Razelle Kurzrock receives research funds from Sequenom, Guardant, Foundation Medicine, Genentech, Pfizer, and Merck Serono, consultant fees from XBiotech and Actuate Therapeutics, and has an ownership interest in Curematch, Inc. Dr. Sandip Patel receives research funding from: Bristol-Myers Squibb, Eli Lilly, Incyte, MedImmune, Pfizer, Roche/Genentech, Xcovery.

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Authors and Affiliations

  1. UCSD-Pfizer Clinical Pharmacology-Oncology Fellow – Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA

    Maulik Patel

  2. Division of Hematology/Oncology, Department of Medicine, University of California, San Diego, Moores Cancer Center, La Jolla, CA, USA

    Sandip Pravin Patel & Razelle Kurzrock

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    Sandip Pravin Patel

  2. Division of Hematology/Oncology Department of Medicine, University of California, San Diego Moores Cancer Center, La Jolla, California, USA

    Razelle Kurzrock

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Patel, M., Patel, S.P., Kurzrock, R. (2018). Combinations of Genomically and Immune-Targeted Therapies in Early-Phase Clinical Trials. In: Patel, S., Kurzrock, R. (eds) Early Phase Cancer Immunotherapy . Current Cancer Research. Springer, Cham. https://doi.org/10.1007/978-3-319-63757-0_9

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