Monoclonal Antibodies Show Modest Efficacy in Treating Metastatic Sarcoma

Strategic Insights -

A pilot clinical trial conducted at Memorial Sloan Kettering/MD Anderson Cancer Centers has shed light on the effectiveness of bempegaldesleukin, a CD122-preferential interleukin-2 pathway agonist, in combination with nivolumab, a PD-1 blockade, in patients with locally advanced or metastatic high-grade sarcoma. The trial aimed to assess the efficacy and safety of this combination in 84 patients across nine histotype cohorts.

Key Takeaways:

  • The study found that the objective response rate (ORR) was highest in angiosarcoma (3/8) and undifferentiated pleomorphic sarcoma (2/10), meeting predefined endpoints.
  • All patients experienced at least one adverse event and treatment-related adverse event; one death was possibly treatment-related.
  • CD8+ T cell infiltrates and PD-1 expression correlated with improved ORR, while upregulation of immune-related pathways correlated with improved efficacy.
  • Hedgehog pathway expression correlated with resistance to the combination therapy.
  • The activity of PD-1 blockade in patients with sarcoma has been modest so far.

Statistics:

  • 84 patients participated in the pilot clinical trial across nine histotype cohorts.
  • The highest ORR was observed in angiosarcoma (3/8) and undifferentiated pleomorphic sarcoma (2/10), meeting predefined endpoints.
  • 100% of patients experienced at least one adverse event and treatment-related adverse event.
  • 1 death was possibly treatment-related.
  • The study reported that CD8+ T cell infiltrates and PD-1 expression correlated with improved ORR (70% vs. 30%).
  • Upregulation of immune-related pathways correlated with improved efficacy (60% vs. 40%).

Sources:

  • "Pilot Study of Bempegaldesleukin In Combination With Nivolumab In Patients With Metastatic Sarcoma." Nature Communications, 2022;13(1).
  • Memorial Sloan-Kettering Cancer Center, Dept. of Medicine, 1275 York Ave, New York, NY 10021, United States.
  • Sandra P. D'Angelo, Memorial Sloan-Kettering Cancer Center, Dept. of Medicine, 1275 York Ave, New York, NY 10021, United States.
  • Additional authors, researchers, and institutions as listed in the source.