nivolumab

Ligand id: 7335

Name: nivolumab

No information available.
Summary of Clinical Use
In December 2014 nivolumab was approved under the FDA's accelerated approval program for the treatment of advanced (metastatic) melanoma, following review of positive clinical trial results [13]. The FDA expanded nivolumab's approval in 2015 to include treatment of advanced (metastatic) squamous and non-squamous non-small cell lung cancer (NSCLC) in patients with disease progression on or after platinum-based chemotherapy. Nivolumab outperformed standard chemotherapy with everolimus, in a randomized, open-label, phase III clinical study in patients with previously treated renal-cell carcinoma [12]. Consequently, in November 2015, FDA approval was extended further to include treatment of advanced renal cell carcinoma in patients who have received prior anti-angiogenic therapy.

Combination therapy with ipilimumab and nivolumab has been reported to exhibit >60% objective-response rate (ORR) in treatment-naive advanced melanoma patients with BRAF wild-type tumours [15] (results from Phase 1 study NCT01927419). This is in comparison to ipilimumab alone which provided only 11% confirmed ORR. These findings have been confirmed by Phase 3 study (NCT01844505) results showing significantly longer progression-free survival in patients given the combination therapy vs. the nivolumab only group [10]. Combination ipilimumab/nivolumab therapy has been FDA approved (2015) for the treatment of patients with BRAF V600 wild-type, unresectable or metastatic melanoma [2,10].

In May 2016, the FDA granted accelerated approval for nivolumab to be used as a therapy for patients with classical Hodgkin lymphoma (cHL) that has relapsed or progressed after autologous hematopoietic stem cell transplantation (HSCT) and post-transplantation brentuximab vedotin. In November 2016, the FDA further expanded approval to include treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) with disease progression on or after a platinum-based therapy.

February 2017 saw accelerated approval for locally advanced or metastatic urothelial carcinoma, for those patients with disease progression despite receiving platinum-containing chemotherapy. The accelerated approval programme saw nivolumab's authorisation as a treatment for paediatric patients, 12 years and older, with mismatch repair deficient (dMMR) and microsatellite instability high (MSI-H) metastatic colorectal cancer that has progressed following treatment with a fluoropyrimidine, oxaliplatin, and irinotecan, in August 2017. Accelerated approval was granted by the FDA in September 2017 for the treatment of patients with hepatocellular carcinoma who have been previously treated with sorafenib, based on preliminary results from clinical trial NCT01658878.
Mechanism Of Action and Pharmacodynamic Effects
Nivolumab binds to the programmed cell death 1 (PD-1, PDCD1) receptor on activated T cells and prevents receptor activiation 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 [3,7,16], and this permits these malignant cells to 'evade' destruction by the immune system. By preventing binding of the cancer cell-derived PD-L1, nivolumab restores local immune detection/destruction by T cells. The mechanism of action by which this antibody works has potential to be a useful strategy in treating many different types of cancer [1,5-6]. The list of clinical trials assessing the efficacy of this treatment testify to its potential usefulness. Click here to view nivolumab trials registered with ClinicalTrials.gov.
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