The concept of blocking PD-1 and PD-L1 for the treatment of cancer was first published in 2001.[6] Pharmaceutical companies began attempting to develop drugs to block these molecules, and the first clinical trial was launched in 2006, evaluating nivolumab. As of 2017, more than 500 clinical trials involving PD-1 and PD-L1 inhibitors have been conducted in more than 20,000 patients.[7] By the end of 2017, PD-1/PD-L1 inhibitors had been approved for the treatment of nine forms of cancer.[8]
PD-1[edit]
Pembrolizumab (formerly MK-3475 or lambrolizumab, Keytruda) was developed by Merck and first approved by the Food and Drug Administration in 2014 for the treatment of melanoma. It was later approved for metastatic non-small cell lung cancer and head and neck squamous cell carcinoma. In 2017, it became the first immunotherapy drug approved for use based on the genetic mutations of the tumor rather than the site of the tumor. It was shown, that patients with higher non-synonymous mutation burden in their tumors respond better to the treatment. Both their objective response rate and progression-free survival) was shown to be higher than in patients with low non-synonymous mutation burden.[11] This suggests that tobacco smoking, due to its high carcinogenicity,[12] not only causes promotion of cancer (in case of non-small-cell lung carcinoma), but also increases chances of the immune system to recognize and attack to the tumor.
Nivolumab (Opdivo) was developed by Bristol-Myers Squibb and first approved by the FDA in 2014 for the treatment of melanoma. It was later approved for squamous cell lung cancer, renal cell carcinoma, and Hodgkin's lymphoma.
Experimental[edit]
As of 2017, at least five PD-1 inhibitors were under development.[7]
- pidilizumab, by Cure Tech
- AMP-224, by GlaxoSmithKline
- AMP-514, by GlaxoSmithKline
- PDR001, by Novartis
- cemiplimab, by Regeneron and Sanofi[13]
PD-L1[edit]
Atezolizumab (Tecentriq) is a fully humanised IgG1 (immunoglobulin 1 antibody developed by Roche Genentech. In 2016, the FDA approved atezolizumab for urothelial carcinoma and non-small cell lung cancer.
Avelumab (Bavencio) is a fully human IgG1 antibody developed by Merck Serono and Pfizer. Avelumab is FDA approved for the treatment of metastatic merkel-cell carcinoma. It failed phase III clinical trials for gastric cancer.[14]
Durvalumab (Imfinzi) is a fully human IgG1 antibody developed by AstraZeneca. Durvalumab is FDA approved for the treatment of urothelial carcinoma and unresectable non-small cell lung cancer after chemoradiation.[15]
Experimental[edit]
At least two PD-L1 inhibitors are in the experimental phase of development.
- BMS-936559, by Bristol-Myers Squibb
- CK-301, by Checkpoint Therapeutics[16]
