Pilot study of bempegaldesleukin in combination with nivolumab in patients with metastatic sarcoma

Nat Commun. 2022 Jun 16;13(1):3477. doi: 10.1038/s41467-022-30874-8.


PD-1 blockade (nivolumab) efficacy remains modest for metastatic sarcoma. In this paper, we present an open-label, non-randomized, non-comparative pilot study of bempegaldesleukin, a CD122-preferential interleukin-2 pathway agonist, with nivolumab in refractory sarcoma at Memorial Sloan Kettering/MD Anderson Cancer Centers (NCT03282344). We report on the primary outcome of objective response rate (ORR) and secondary endpoints of toxicity, clinical benefit, progression-free survival, overall survival, and durations of response/treatment. In 84 patients in 9 histotype cohorts, all patients experienced ≥1 adverse event and treatment-related adverse event; 1 death was possibly treatment-related. ORR was highest in angiosarcoma (3/8) and undifferentiated pleomorphic sarcoma (2/10), meeting predefined endpoints. Results of our exploratory investigation of predictive biomarkers show: CD8 + T cell infiltrates and PD-1 expression correlate with improved ORR; upregulation of immune-related pathways correlate with improved efficacy; Hedgehog pathway expression correlate with resistance. Exploration of this combination in selected sarcomas, and of Hedgehog signaling as a predictive biomarker, warrants further study in larger cohorts.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents, Immunological* / therapeutic use
  • Hedgehog Proteins
  • Humans
  • Interleukin-2 / therapeutic use
  • Neoplasms, Second Primary* / chemically induced
  • Nivolumab / therapeutic use
  • Pilot Projects
  • Programmed Cell Death 1 Receptor / metabolism
  • Sarcoma* / drug therapy
  • Sarcoma* / pathology


  • Antineoplastic Agents, Immunological
  • Hedgehog Proteins
  • Interleukin-2
  • Programmed Cell Death 1 Receptor
  • Nivolumab

Associated data

  • ClinicalTrials.gov/NCT03282344