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Synonyms: NKTR-214 | NKTR214
Compound class:
Peptide or derivative
Comment: Bempegaldesleukin (NKTR-214) is an engineered variant of human interleukin-2 [4] in which Ala1 has been removed and Cys125 is substituted by Ser. The peptide is produced in E. coli and an average of 6 lysine residues are N6 substituted with [(2,7-bis{[methylpoly(oxyethylene)]carbamoyl}-9H-fluoren-9-yl)methoxy]carbonyl (PEG-Lys). In the PEG-bound form the IL-2 is inactive, but In vivo the PEG chains are released slowly which provides a more controlled release of active IL-2 peptide [4] (the IL-2 conjugates with 1 or 2 PEG chains are the most biologically active conjugates [3]). This prodrug strategy mitigates against the severe side effects which limit maximal dosing of parental aldesleukin.
Ligand Activity Visualisation ChartsThese are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts. ✖ |
| No information available. |
Summary of Clinical Use  |
| Bempegaldesleukin (NKTR-214) has progressed to Phase 3 evaluation in treatment naive/inoperable or metastatic melanoma, and advanced/metastatic renal cell carcinoma (RCC). Both of these trials are combining NKTR-214 with PD-1 checkpoint blockade using nivolumab. In addition, the RCC study is comparing the NKTR-214/checkpoint inhibitor combination with kinase inhibitor monotherapy (with either sunitinib or cabozantinib). Earlier stage trials in other solid tumour types are also onging. Click here to link to ClinicalTrials.gov's full list of NKTR-214 studies. In August 2019, the FDA granted breakthrough therapy designation to bempegaldesleukin + nivolumab for the initial treatment of unresectable or metastatic melanoma. |
| Clinical Trials | |||||
| Clinical Trial ID | Title | Type | Source | Comment | References |
| NCT03729245 | A Study of NKTR-214 in Combination With Nivolumab Compared With the Investigator's Choice of a Tyrosine Kinase Inhibitor (TKI) Therapy (Either Sunitinib or Cabozantinib Monotherapy) for Advanced Metastatic Renal Cell Carcinoma (RCC) | Phase 3 Interventional | Nektar Therapeutics | ||
| NCT03635983 | A Study of NKTR-214 Combined With Nivolumab vs Nivolumab Alone in Participants With Previously Untreated Inoperable or Metastatic Melanoma | Phase 3 Interventional | Bristol-Myers Squibb | ||
