What are the targets of joint PD-1/PD-L1 therapy that are of concern?

The number of clinical trials doubled in 2020, and combination therapy became mainstream in clinical trials As of September 2020, a total of about 4,400 clinical trials were testing anti-PD-1/PD-L1 monoclonal antibodies, of which 3,674 were active.
number of clinical trials has tripled compared to September 2017.
note that the number of clinical trials increased by 1,358 between 2019 and 2020, almost the same increase as in 2017-2019 (1,539).
further analysis of clinical trial characteristics found that more than 80% of clinical trials were testing combination therapies consisting of anti-PD-1/PD-L1 antibodies and other therapies.
in all stages of clinical development, clinical trials of test combination therapies are growing faster than anti-PD-1/PD-L1 monotherapy.
further analysis of trends in clinical trial trends against PD-1/PD-L1 monoclonal antibody trials in 2017 and 2020 shows that the number of new clinical trials evaluating monopdrial therapies per year has been declining since 2017, while the number of new clinical trials evaluating combination therapies has been increasing.
and the number of planned enrollments for clinical trials is declining, with the average number of patients enrolled in clinical trials testing monodring dropping from 854 in 2014 to 131 in 2020 (more than 500 percent), while the number of combined therapies registered has fallen by 40 percent.
researchers point out that one reason for the declining enrollment may be that clinical trials are moving toward using biomarkers for patient screening, which in part slows patient enrollment and reduces the number of patients that clinical trials need to recruit.
number of new start-up clinical trials (bar chart) and patient program enrollment (line chart) (Photo Source: Resources) Which are the popular targets for combination therapy? As anti-PD-1/PD-L1 clinical trials migrate to combination therapies, which targets are popular targets for combination therapies? The researchers' analysis showed that in addition to PD-1/PD-L1, clinical trials included 253 drug target groups, an increase of 129 new target groups compared to 2017.
Over the past 10 years, targeted therapies targeted at VEGF/VEGFR, chemotherapy and targeted therapies targeted at CTLA-4 have been the primary options for combining therapies with anti-PD-1/PD-L1 antibodies.
And VEGF/VEGFR combined therapy with PD-1/PD-L1 antibodies has become the most common combination therapy in clinical trials in the first three quarters of this year, with 154 new clinical trials testing this combination, surpassing chemotherapy (145) and anti-CTLA-4 therapy (64).
in addition to these three types of therapies, emerging targets for combination therapies include PARP inhibitors, targeted TIGIT, TGF beta/TGFR, TLRs, and lysovirus and cancer vaccines.
2018 Cancer Institute report noted that while the number of clinical trials of PD-1/PD-L1 antibody combination therapy targeted in anti-PD-1/PD-L1 antibody combination therapy (Photo Source: Reference 1)) generally declined, the 2018 Cancer Institute report noted that while the number of clinical trials of PD-1/PD-L1 antibody trials is rising rapidly, the rate of patient recruitment is declining.
may be caused by a number of factors, including rapid changes in care standards, increased screening of patients using biomarkers, and competition from similar trials for a relatively small group of subjects.
and this year's rate of patient recruitment has declined globally compared to 2019.
coVID-19 epidemic may be one of the main reasons for reducing patient registration.
china is still recruiting patients faster than the rest of the world because of its large cancer base.
, the shift from clinical trials to combination therapies is also reflected in the rate of patient recruitment.
clinical trials of PD-1/PD-L1 antibody monotherapy decreased by 41% compared to 2020 compared to 2019, while the recruitment rate of combination therapies increased by 18%.
the recruitment rate of clinical trials of anti-PD-1/PD-L1 antibody monodreses and combination therapies around the world in 2019 and 2020 (Photo source: Resources. The 19 pandemic affects all aspects of clinical trials, and although its potential impact on PD-1/PD-L1 clinical research and development pipelines is not yet fully apparent, it is foreseeable that the pandemic played a role in the decrease in patient enrollment and the suspension of some clinical trials.
This year's clinical trial analysis shows that combination therapies have become mainstream in clinical development, and that the field of cancer immunology is shifting from combinations based on chemotherapy or anti-CTLA-4 therapies to other targeted therapies that overcome cancer resistance mechanisms, including targeted angiogenesic drugs and innovative double immunotherapy combinations.
reference: s1. Upadhaya et al., (2020). Combinations take centre stage in PD1/PDL1 inhibitor clinical trials. Nature Reviews Drug Discovery, doi: [2] CRI: PD-1/PD-L1 landscape. Retrieved November 18, 2020, from。