Bempegaldesleukin plus nivolumab in untreated, unresectable or metastatic melanoma: Phase III PIVOT IO 001 study design

Future Oncol. 2020 Oct;16(28):2165-2175. doi: 10.2217/fon-2020-0351. Epub 2020 Jul 29.


Nivolumab, a PD-1 inhibitor, has demonstrated prolonged survival benefit in patients with advanced melanoma. Bempegaldesleukin (BEMPEG; NKTR-214), a first-in-class CD122-preferential IL-2 pathway agonist, provides sustained signaling through the IL-2βγ receptor, which activates effector T and natural killer cells. In the Phase I/II PIVOT-02 trial, the combination of bempegaldesleukin plus nivolumab was well-tolerated and demonstrated clinical activity as first-line therapy in metastatic melanoma. Here, we describe the design of and rationale for the Phase III, global, randomized, open-label PIVOT IO 001 trial comparing bempegaldesleukin plus nivolumab with nivolumab alone in patients with previously untreated, unresectable or metastatic melanoma. Primary end points include objective response rate, progression-free survival and overall survival. Key secondary end points include further investigation of safety/tolerability, previously assessed in the PIVOT-02 trial. Clinical Trial Registration: NCT03635983 (

Keywords: I-O combinations; IL-2 pathway; NKTR-214; bempegaldesleukin; complete response; immuno-oncology; metastatic melanoma; nivolumab.

Publication types

  • Clinical Trial, Phase III

MeSH terms

  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor
  • Clinical Protocols*
  • Female
  • Humans
  • Male
  • Melanoma / drug therapy*
  • Melanoma / etiology
  • Melanoma / pathology*
  • Molecular Targeted Therapy
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Nivolumab / administration & dosage
  • Research Design


  • Antineoplastic Agents, Immunological
  • Biomarkers, Tumor
  • Nivolumab

Associated data