pembrolizumab

Ligand id: 7499

Name: pembrolizumab

No information available.
Summary of Clinical Use
The US FDA granted pembrolizumab priority review designation in June 2014 following very encouraging clinical trial results which were presented at the American Society of Clinical Oncology 50th Annual Meeting in Chicago, 2014. Lyle et al. (J Clin Oncol 32:5s, 2014 (suppl; abstr 9077)) reported complete remission of 52% of metastatic tumours in patients with advanced malignant melanoma, the remission rate was highest in lung metastases. In early September of the same year, the antibody was approved as a therapy for patients with advanced or unresectable melanoma who are no longer responding to other drugs.
Further clinical trials are still ongoing, testing the efficacy of this antibody, as either a monotherapy or in combination with other anti-neoplastics, across a range of more than 30 different cancer types. Click here to view these trials at ClinicalTrials.gov.

In October 2014, the US FDA granted Breakthrough Therapy Designation for pembrolizumab to be used to treat advanced non-small cell lung cancer (NSCLC), in particular for NSCLC which is epidermal growth factor receptor (EGFR) mutation negative, or anaplastic lymphoma kinase (ALK) rearrangement-negative and which has progressed during or following platinum-based chemotherapy. This was granted in response to data from the Phase Ib clinical trial NCT01295827 (KEYNOTE-001). Click here to link to ClinicalTrials.gov's list of active Phase II and III pembrolizumab/NSCLC trials.

In December 2015, FDA approval was granted for pembrolizumab use to include first-line therapy for unresectable or metastatic melanoma.

Results of a Phase 2 clinical trial (NCT02267603) suggest that pembrolizumab may be effective in the treatment of the rare skin cancer, Merkel cell carcinoma (MCC) [5].

In August 2016, the US FDA granted pembrolizumab injection accelerated approval for the treatment of patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy. A multicenter, randomized trial is ongoing to ascertain pembrolizumab's superiority over standard therapy and to elucidate its clinical benefit. In October 2016 FDA approval was expanded to include first-line treatment of metastatic PD-L1-expressing NSCLC (as determined by an FDA-approved test).

In March 2017, the FDA expanded approval to include treatment of adult and pediatric patients with refractory classical Hodgkin lymphoma (cHL), or who have relapsed after three or more prior lines of therapy. FDA accelerated approval was granted in May 2017 for the treatment of previously untreated metastatic non-squamous NSCLC (in combination with pemetrexed and carboplatin). Further approval expansion in May 2017 covers the use of pembrolizumab to treat locally advanced or metastatic urothelial carcinoma that has progressed during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy. Later in May 2017, accelerated approval was granted for the treatment of adult and pediatric patients with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors (notably in any tissue) that have progressed following prior treatment and who have no satisfactory alternative treatment options, or with MSI-H or dMMR colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.
Mechanism Of Action and Pharmacodynamic Effects
Like nivolumab, pembrolizumab binds to the programmed cell death 1 (PD-1, PDCD1) receptor on activated T cells [3] and prevents receptor activation by endogenous ligands PD-L1 and PD-L2. PD-L1 has an immuno-inhibitory effect on T cells, whereby activation of PD-1 by PD-L1 results in T cell death or quiescence. Many cancer cells express PD-L1 [2,4,6], and this permits these malignant cells to 'evade' destruction by the immune system. By preventing binding of the cancer cell-derived PD-L1, pembrolizumab restores local immune detection/destruction by T cells.
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