Trials for Cancer Immunotherapies Grow Significantly From 2017 to 2021

While the number of trials for cancer immunotherapies grew significantly, combination therapies being studied increased while monotherapies decreased.

The number of clinical trials testing PD1/PD-L1 inhibitor therapies has increased significantly since 2017 and may be outstripping patient demand, according to an analysis from the Cancer Research Institute (CRI).

Since 2017, the annual number of clinical trials including an agent that targets PD1/PD-L1 increased 278%, reaching 5683 trials worldwide. The findings were published in Nature Reviews Drug Discovery.1

The analysis of the landscape found there are 1481 trials with pembrolizumab, 1227 with nivolumab, 538 with durvalumab, 512 with atezolizumab, 215 with avelumab, 67 with cemiplimab, 12 with dostarlimab, and 1631 with other therapies, such as any anti–PD1/PD-l1 monoclonal antibody.

There are 300 targets and pathways being testing, which is an 18% increase since the last report in 2020, according to CRI.

In addition, the number of monotherapies being studied is on the decline while the number of combination studies is on the rise. In 2020, 90% of the new trials started were for combination therapies.

The combination trials are testing PD1/PD-L1–blocking immunotherapies in combination with other immunotherapies, targeted therapy, chemotherapy, and radiation.

The authors also noted that bispecific antibodies represent a significant area of growth. In combination trials, bispecific antibodies “interrogate 28 different targets/mechanisms including checkpoint pathways other than PD1/PDL1.”

“Planned patient enrollment in monotherapy trials has been falling precipitously, a seven-fold decrease since 2014, while combination trial enrollment projections have seen less than a two-fold drop since 2015,” according to CRI.

In 2021, Richard Pazdur, MD, director of the FDA's Oncology Center of Excellence (OCE), and Julie Beaver, MD, chief of medical oncology of OCE, wrote in New England Journal of Medicine that the “rapid expansion of the checkpoint inhibitor class has largely been uncoordinated.”2 They added that the FDA is cautioning against single-arm trials in patients with refractory disease for checkpoint inhibitors.

Pazdur and Beaver also called checkpoint inhibitor drug development the “Wild West” and noted that the FDA is encouraging collaboration among drug sponsors.

“Harnessing these redundant efforts will lead to greater efficiency in drug development, not only reducing development costs, but also protecting our most vital resources — patients and their confidence in the clinical trial system.


1. Upadhaya S, Neftelino ST, Hodge J, Campbell J. Challenges and opportunities in the PD1/PDL1 inhibitor clinical trial landscape. Nat Rev Drug Discov. Published online February 10, 2022. doi:10.1038/d41573-022-00030-4

2. Beaver JA, Pazdur R. The Wild West of checkpoint inhibitor development. N Engl J Med. Published online December 15, 2021. doi:10.1056/NEJMp2116863

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