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Phase 2 study of pembrolizumab in patients with recurrent and residual high-grade meningiomas

Author

Listed:
  • Priscilla K. Brastianos

    (Harvard Medical School)

  • Albert E. Kim

    (Harvard Medical School)

  • Anita Giobbie-Hurder

    (Harvard Medical School)

  • Eudocia Quant Lee

    (Harvard Medical School)

  • Nancy Wang

    (Harvard Medical School)

  • April F. Eichler

    (Harvard Medical School)

  • Ugonma Chukwueke

    (Harvard Medical School)

  • Deborah A. Forst

    (Harvard Medical School)

  • Isabel C. Arrillaga-Romany

    (Harvard Medical School)

  • Jorg Dietrich

    (Harvard Medical School)

  • Zachary Corbin

    (Smilow Cancer Hospital and Yale Cancer Center, Yale School of Medicine)

  • Jennifer Moliterno

    (Smilow Cancer Hospital and Yale Cancer Center, Yale School of Medicine)

  • Joachim Baehring

    (Smilow Cancer Hospital and Yale Cancer Center, Yale School of Medicine)

  • Michael White

    (University of Rochester, Division of Neuro-Oncology)

  • Kevin W. Lou

    (Harvard Medical School)

  • Juliana Larson

    (Harvard Medical School)

  • Magali A. Sauvage

    (Harvard Medical School)

  • Kathryn Evancic

    (Harvard Medical School)

  • Joana Mora

    (Harvard Medical School)

  • Naema Nayyar

    (Harvard Medical School)

  • Jay Loeffler

    (Harvard Medical School)

  • Kevin Oh

    (Harvard Medical School)

  • Helen A. Shih

    (Harvard Medical School)

  • William T. Curry

    (Harvard Medical School)

  • Daniel P. Cahill

    (Harvard Medical School)

  • Fred G. Barker

    (Harvard Medical School)

  • Elizabeth R. Gerstner

    (Harvard Medical School)

  • Sandro Santagata

    (Harvard Medical School
    Harvard Medical School
    Ludwig Center at Harvard)

Abstract

High-grade meningiomas are associated with neuro-cognitive morbidity and have limited treatments. High-grade meningiomas harbor an immunosuppressive tumor microenvironment (TME) and programmed death-ligand 1 (PD-L1) expression may contribute to their aggressive phenotype. Here, we present the results of a single-arm, open-label phase 2 trial (NCT03279692) evaluating the efficacy of pembrolizumab, a PD-1 inhibitor, in a cohort of 25 evaluable patients with recurrent and progressive grade 2 and 3 meningiomas. The primary endpoint is the proportion of patients alive and progression-free at 6 months (PFS-6). Secondary endpoints include progression-free and overall survival, best intracranial response, and toxicity. Our study has met its primary endpoint and achieved a PFS-6 rate of 0.48 (90% exact CI: 0.31–0.66) and a median PFS of 7.6 months (90% CI: 3.4–12.9 months). Twenty percent of patients have experienced one (or more) grade-3 or higher treatment-related adverse events. These results suggest that pembrolizumab exerts promising efficacy on a subset of these tumors. Further studies are needed to identify the biological facets within the meningioma TME that may drive response to immune-based therapies.

Suggested Citation

  • Priscilla K. Brastianos & Albert E. Kim & Anita Giobbie-Hurder & Eudocia Quant Lee & Nancy Wang & April F. Eichler & Ugonma Chukwueke & Deborah A. Forst & Isabel C. Arrillaga-Romany & Jorg Dietrich & , 2022. "Phase 2 study of pembrolizumab in patients with recurrent and residual high-grade meningiomas," Nature Communications, Nature, vol. 13(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29052-7
    DOI: 10.1038/s41467-022-29052-7
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