Development of PD-1 and PD-L1 inhibitors as a form of cancer immunotherapy: a comprehensive review of registration trials and future considerations

By J. Gong, Alexander Chehrazi-Raffle, S. Reddi, Ravi Salgia. Journal of Immunotherapy for Cancer, 2018

1,141 citations recorded by the source corpus.

Early preclinical evidence provided the rationale for programmed cell death 1 (PD-1) and programmed death ligand 1 (PD-L1) blockade as a potential form of cancer immunotherapy given that activation of the PD-1/PD-L1 axis putatively served as a mechanism for tumor evasion of host tumor antigen-specific T-cell immunity. Early-phase studies investigating several humanized monoclonal IgG4 antibodies targeting PD-1 and PD-L1 in advanced solid tumors paved way for the development of the first PD-1 inhibitors, nivolumab and pembrolizumab, approved by the Food and Drug Administration (FDA) in 2014. The number of FDA-approved agents of this class is rapidly enlarging with indications for treatment spanning across a spectrum of malignancies. The purpose of this review is to highlight the clinical development of PD-1 and PD-L1 inhibitors in cancer therapy to date. In particular, we focus on detailing the registration trials that have led to FDA-approved indications of anti-PD-1 and anti-PD-L1 therapies in cancer. As the number of PD-1/PD-L1 inhibitors continues to grow, predictive biomarkers, mechanisms of resistance, hyperprogressors, treatment duration and treatment beyond progression, immune-related toxicities, and clinical trial design are key concepts in need of further consideration to optimize the anticancer potential of this class of immunotherapy.

Subfields: Oncology

View Paper: https://www.semanticscholar.org/paper/9f36b0ee5fec349d34c1b2d8dc0bb4ee30c1efcd

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

In Oncology

1. M. Hung
2. J. Hsu
3. Chia‐Wei Li
4. Jong-Ho Cha
5. Li-Chuan Chan

Citations in the corpus

• PD-L1 Immunohistochemistry Comparability Study in Real-Life Clinical Samples: Results of Blueprint Phase 2 Project (2018, background): “Immune checkpoint inhibitor therapies targeting the programmed death 1/programmed death ligand 1 (PDL1) pathway have become part of the standard of care in oncology.(1) At least five inhibitors (nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab) have been approved by drug regulatory b”
• Regulatory mechanisms of PD-1/PD-L1 in cancers (2024, background): “…carcinoma (nivolumab, pembrolizumab, durvalumab, atezolizumab, and avelumab), non-small cell lung cancer (pembro-lizumab, nivolumab, and atezolizumab), renal cell carcinoma (nivolumab), Hodgkin lymphoma (pembro-lizumab and nivolumab), skin squamous cell carcinoma (cemiplimab), and so on [315, 316].”
• Mechanisms controlling PD-L1 expression in cancer (2019, background): “, nivolumab, pembrolizumab and cemiplimab) were developed and have demonstrated promising results in clinical trials for various types of cancer (Gong et al., 2018).”