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Review
. 2016 Apr;9(2):89-104.
doi: 10.1111/cts.12391. Epub 2016 Mar 30.

Immunotherapy and Novel Combinations in Oncology: Current Landscape, Challenges, and Opportunities

K M Morrissey  1 , T M Yuraszeck  2 , C-C Li  1 , Y Zhang  2 , S Kasichayanula  2
Affiliations
Review

Immunotherapy and Novel Combinations in Oncology: Current Landscape, Challenges, and Opportunities

K M Morrissey et al. Clin Transl Sci. 2016 Apr.
No abstract available

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Figures

Figure 1
Figure 1
History of immunotherapy. Key events leading to the development of currently marketed immunotherapies including sipuleucel‐T (Provenge), ipilimumab (Yervoy), blinatumomab (BLINCYTO), nivolumab (Opdivo), pembrolizumab (Keytruda), and talimogene laherparepvec/T‐Vec (Imlygic).
Figure 2
Figure 2
Intervention in the cancer‐immunity cycle by immunotherapy agents. Overcoming resistance and restoring a functional immune‐surveillance system requires leveraging multiple, complementary mechanisms of action and agents that acts in multiple phases of the cancer‐immunity cycle (numbers denote the phases at which each type of immunotherapy acts).
Figure 3
Figure 3
Dose–response contour for rule‐based and model‐based clinical trial designs. Doses explored relative to the dose–toxicity contour using a traditional, rule‐based method vs. a model‐based design. DLT, dose‐limiting toxicity. Trials based on rule‐based designs typically maintain the dose of one agent as a constant while escalating the dose of the other agent, resulting in a narrow exploration of the dose–toxicity contour. Trials utilizing model‐based designs may vary the doses of both agents to more comprehensively explore the dose–toxicity contour.
Figure 4
Figure 4
The role of modeling and simulation in combination immunotherapy development. (a) Modeling and simulation approaches used to answer questions during preclinical and clinical development and life‐cycle management. (b) Iterative cycle between experimentation, modeling, prediction, analysis, and the generation of new, testable hypotheses. LCM, life‐cycle management; FIH, first‐in‐human; PD, pharmacodynamics; PKPD, pharmacokinetics/pharmacodynamics; PBPK model, physiologically based pharmacokinetic model; DDI, drug–drug interaction.
See this image and copyright information in PMC

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