PD-1 and PD-L1 inhibitors

[6] Pharmaceutical companies began attempting to develop drugs to block these molecules, and the first clinical trial was launched in 2006, evaluating nivolumab.

The FDA has approved several assays to measure the level of PD-L1 expressed by tumor cells, in order to predict the likelihood of response to an inhibitor.

Both their objective response rate and progression-free survival was shown to be higher than in patients with low non-synonymous mutation burden.

Dostarlimab (Jemperli) – was developed by GlaxoSmithKline and was first approved for the treatment of mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer by the FDA in April of 2021.

[16] On August 17, 2021, the FDA granted accelerated approval for the treatment of mismatch repair deficient (dMMR) recurrent or advanced solid tumors.

[17] Retifanlimab (Zynyz) was developed by Incyte and first granted accelerated approval by the FDA in March 2023 for the treatment of Merkel cell carcinoma (MCC).

Durvalumab is FDA approved for the treatment of urothelial carcinoma and unresectable non-small cell lung cancer after chemoradiation.

[33] Cosibelimab (Unloxcyt) by Checkpoint Therapeutics is a PD-L1 inhibitor developed by Dana Farber, and was approved in the United States in December 2024 for cutaneous squamous cell carcinoma.

The combination of PD-1/PD-L1 inhibitors and type I interferons has shown promise in preclinical and clinical studies (phases I and II).

Some of these include interstitial pneumonitis,[40] colitis, hepatitis, thyroiditis, skin reactions, low levels of platelets and white blood cells, inflammation of the brain or spinal cord, neuromuscular adverse events[41] including myositis, Guillain-Barré syndrome, myasthenia gravis; myocarditis and cardiac insufficiency, acute adrenal insufficiency, and nephritis.

[47] When compared with standard chemotherapeutic agents, PD-1/PD-L1 inhibitors had a lower reported incidence of fatigue, sensory neuropathy, diarrhea, bone marrow suppression, loss of appetite, nausea, and constipation.