Pilot study of bempegaldesleukin in combination with nivolumab in patients with metastatic sarcoma. Academic Article uri icon

Overview

abstract

  • 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.

authors

publication date

  • June 16, 2022

Research

keywords

  • Antineoplastic Agents, Immunological
  • Neoplasms, Second Primary
  • Sarcoma

Identity

PubMed Central ID

  • PMC9203519

Scopus Document Identifier

  • 85132275841

Digital Object Identifier (DOI)

  • 10.18637/jss.v033.i01

PubMed ID

  • 35710741

Additional Document Info

volume

  • 13

issue

  • 1