4,400 clinical trials are under study worldwide! The latest trend of PD-1/PD-L1 at the top of the wind is worth turning off

"PD-1 into innovative drug Waterloo," "disappearing PD-100 billion market," "PD-1 drug companies encounter black swans" ... Recently in the public opinion of the PD-1 market, really can be said to be a wave of uneven another wave.
behind this, or the inevitable result of the homogenization of local PD-1, is an inevitable episode in the process of commercialization, and is also a signal that the innovation power of local pharmaceutical companies needs to be further broken.
, if you jump out of the local market and look at the global perspective, what is the current PD-1 research and development picture? A recent report, "Combins take center stage in PD-1/PD-L1 resedor clinical trials", published in the journal Nature Reviews Drug Discovery, led by several researchers at the American Cancer Institute in association with VIAVIA, summarizes the current state of PD-1/PD-L1 clinical trials worldwide and the challenges in patient recruitment.
we will now organize the main elements of the report as follows.
PD-1 / PD-L1 clinical trials tripled in 20120, according to the latest data, as of September 2020, there were 4,400 PD-1 / PD-L1 monoantial clinical trials under study worldwide, of which 3,674 were active (Figure 1.1).
compared to three years ago (September 2017), the total number of clinical trials for PD-1/PD-L1 monoants increased threefold;
1.1: PD-1 / PD-L1 Antibody Clinical Trials 2017 and 2020; Other PDx includes any PD-1 / PD-L1 Antibody Figures not approved by the FDA 1.2:2017 to 202 Interestingly, the increase in PD-1/PD-L1 monoantial clinical trials in 0 years is that the number of PD-1/PD-L1 clinical trials (Figure 1.2, other PDx), which are in clinical development but not yet FDA approved, shows a greater increase, especially in clinical trials with other therapies.
strongly suggests that the combination of PD-1 / PD-L1 antibodies with other therapies shows great prospects in the clinical development process.
further analysis of the report indicated that 2,949 (80%) of the 3,674 active clinical trials focused on a combination of PD-1/PD-L1 monoantotherapy and IO therapy, targeted therapy, chemotherapy, radiotherapy, etc.
, the increase in the number of clinical trials of PD-1/PD-L1 monoantial combination therapy has outpaced the increase in the number of clinical trials as monotherapies.
The number of clinical trials for single-drug therapy is declining to better understand the progress of PD-1/PD-L1 monoantial trials, and the report tracks changes in the status of clinical trials starting in 2014 and beyond (Figure 2.1), finding that earlier trials have entered the "active, not recruiting" phase, while most trials that only started in 2017 or later are still in the "not yet recruited" or "recruited" phase.
and it is worth noting that since 2017, the number of trials in both phases is greater than the number of completed trials.
2.1: Progress in PD-1 / PD-L1 monotherapy and combined therapy trials for the first three quarters of 2014 to 2020 is also in 2017, PD-1 / The number of new clinical trials of PD-L1 monotherapy has reached a peak of 197, while combined therapy trials continue to increase each year, accounting for nearly 90 per cent of all targeted PD-1/ PD-L1 trials (Figure 2.2).
Figure 2.2: A comparison of monotherapy and combination therapy clinical trials shows that over the past seven years, the average number of planned patients in each single-drug clinical trial fell by as much as 500 percent from 854 in 2014 to 131 in 2020.
, combined therapy clinical trials fell from 187 in 2014 to 111 in 2020, with the average planned patient enrolment dropping by only 40 percent.
side of the overall decline in the average planned patient enrolment rate may be based on an increase in biomarker patient selection, which may slow recruitment and reduce the size of trials.
03 Global Patient Recruitment Trends: China still has the highest patient recruitment rate in 2019, and the report authors calculated patient recruitment rates (RRs) from clinical trial sites in major markets in the U.S., China, Europe, and Asia Pacific, and found that China led the clinical trials of PD-1/PD-L1 single-drug therapy and combined therapy.
, the report updates and re-analyzes the RR in current global PD-1/PD-L1 clinical trials.
report notes that in the past year, RR in clinical trials of PD-1/PD-L1 monopdr drug therapy has declined globally, with China toping the declining rate with 41%, although clinical trials of PD-1/PD-L1 combined therapy in China have increased by 18%, while in all other regions RR has declined significantly or remained unchanged.
these RR trends are consistent with the shift from single-drug therapy trials to combination therapy trials.
Figure 3: Overall, China maintains the highest RR in single-drug treatment and joint trials compared to the median patient recruitment rate in different countries and regions in 2019 and 2020, and the decline in RR in most trials worldwide may be due to the COVID-19 pandemic.
04 New combination therapy options: Chemotherapy, VEGF/VEGFR, CTLA4 Trend towards combination therapy in PD-1/PD-L1 clinical trials, the report further analyzes drug targets in combination therapy.
results show that 253 drug target combinations (excluding PD-1 / PD-L1) are currently in clinical trials, of which 129 new target combinations have been added in the past 3 years.
As can be seen from the figure below, trends in clinical trials of PD-1/PD-L1 combination therapy over the past decade have shown that combinations with chemotherapy and VEGF/VEGFR and CTLA4 targets are the main combination therapy strategies, with the number of studies of chemotherapy and VEGF/VEGFR continuing to increase.
4.1: The main targets of PD-1/PD-L1 combined therapy from 2011 to 2020 are indeed, and from a more in-depth analysis of clinical trials initiated in the first three quarters of 2020, PD-1/PD-The combination of L1 monoantial and VEGF/VEGFR targeted therapies is the most important combination of treatments (154 new trials), surpassing chemotherapy (145 new trials) and anti-CTLA4 (64 new trials) (supplementary Figure 4.2).
next, a combination of PD-1/PD-L1 monoantigen and approved therapies (e.g. PARP inhibitors) as well as growing IO targets and drugs (e.g. TIGIT, TGF beta/TGFR, TLR), lysovirus, cancer vaccines, etc. will be possible.
Figure 4.2: Analysis of PD-1/PD-L1 clinical trials over the past three years by the conclusions of 724 new combined therapy trials initiated in 2020 shows that clinical trials moving from single-drug therapy to combined therapy are growing rapidly and this trend has received widespread attention.
Currently, not only do combination therapy trials account for a large part of the drug mix, but the drug mix is also shifting from the use of chemotherapy and anti-CTLA4 combinations to other targeted methods (e.g., angiogenesic targeting drugs and new IO-IO combinations) to bypass drug resistance mechanisms for greater efficacy of PD-1/PD-L1.
But on the other side of the growth in PD-1/PD-L1 clinical trials, global patient recruitment rates are declining and recruitment for new trials is stagnating, which is one of the reasons behind the COVID-19 pandemic or the decline in patient enrolment and trial stagnation.
, however, the ongoing assessment of the global landscape of PD-1/PD-L1 clinical trials remains critical to determining new trends in this area in the future.