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. 2018 Mar 13;7(4):e1408744.
doi: 10.1080/2162402X.2017.1408744. eCollection 2018.

Combination therapy with PD-1/PD-L1 blockade: An overview of ongoing clinical trials

C Bryce Johnson  1   2 , Shwe Y Win  1
Affiliations

Combination therapy with PD-1/PD-L1 blockade: An overview of ongoing clinical trials

C Bryce Johnson et al. Oncoimmunology. .

Abstract

Monoclonal antibodies (mAbs) that block the programmed death 1 (PD-1) or programmed death-ligand 1 (PD-L1) receptors are the most clinically advanced tumor immunotherapies. Given the broad antitumor efficacy and novel mechanism of action, numerous combinatorial approaches incorporating PD-1/PD-L1 blockade have been suggested; herein we present a comprehensive analysis of these clinical trials. We queried clinicaltrials.gov for all PD-1/PD-L1 mAbs administered for cancer therapy with an end date of 4/30/2017. A total of 1,218 clinical trials met our search criteria. These trials have a planned enrollment of 227,190 patients, and approximately half (493) were initiated in 2016 alone. Of these over 1,200 trials, 916 combine PD-1/PD-L1 blockade with at least one additional therapy, ranging from traditional treatment modalities like surgery and chemoradiation to newer therapies like small molecule inhibitors and other immunotherapies. The staggering proliferation of clinical trials combining PD-1/PD-L1 blockade with disparate treatments necessitates careful accounting to maximize efficiency and highlight areas of unmet needs. We believe our analysis provides this data and expect it will facilitate the design of future clinical trials in this burgeoning area of oncology research.

Keywords: Cancer immunotherapy; PD-1; PD-L1; T cell checkpoint inhibitors; clinical trials.

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Figures

Figure 1.
Figure 1.
Overview of PD-1/PD-L1 trials. A, number of trials initiated by year. B, number of trials by antibody. C, number of trials initiated by site of tumor. ASTs = advanced solid tumors.
Figure 2.
Figure 2.
Overview of combination PD-1/PD-L1 trials. A, number of trials listed according to number of therapies combined with PD-1/PD-L1 blockade (e.g. trials with 2 combination therapies add 2 additional agents to PD-1/PD-L1 blockade). B, number of combination trials grouped broadly by treatment modality/mechanism of action.
Figure 3.
Figure 3.
Analysis of trials combining tumor-targeted agents or immunotherapies with PD-1/PD-L1 blockade. Number of trials listed according to mechanism of action for A, tumor-targeted therapies, and B, non-CTLA-4 immunotherapies.
See this image and copyright information in PMC

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