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

Author

Listed:
  • Sandra P. D’Angelo

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College
    Parker Institute for Cancer Immunotherapy, Memorial Sloan Kettering Cancer Center)

  • Allison L. Richards

    (Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center)

  • Anthony P. Conley

    (The University of Texas MD Anderson Cancer Center)

  • Hyung Jun Woo

    (Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center)

  • Mark A. Dickson

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

  • Mrinal Gounder

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

  • Ciara Kelly

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

  • Mary Louise Keohan

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

  • Sujana Movva

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

  • Katherine Thornton

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

  • Evan Rosenbaum

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

  • Ping Chi

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

  • Benjamin Nacev

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College
    Laboratory of Chromatin Biology and Epigenetics, The Rockefeller University)

  • Jason E. Chan

    (Memorial Sloan Kettering Cancer Center)

  • Emily K. Slotkin

    (Memorial Sloan Kettering Cancer Center)

  • Hannah Kiesler

    (Memorial Sloan Kettering Cancer Center)

  • Travis Adamson

    (Memorial Sloan Kettering Cancer Center)

  • Lilan Ling

    (Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center)

  • Pavitra Rao

    (Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center)

  • Shreyaskumar Patel

    (The University of Texas MD Anderson Cancer Center)

  • Jonathan A. Livingston

    (The University of Texas MD Anderson Cancer Center)

  • Samuel Singer

    (Memorial Sloan Kettering Cancer Center)

  • Narasimhan P. Agaram

    (Memorial Sloan Kettering Cancer Center)

  • Cristina R. Antonescu

    (Memorial Sloan Kettering Cancer Center)

  • Andrew Koff

    (Program in Molecular Biology, Memorial Sloan Kettering Cancer)

  • Joseph P. Erinjeri

    (Memorial Sloan Kettering Cancer Center)

  • Sinchun Hwang

    (Memorial Sloan Kettering Cancer Center)

  • Li-Xuan Qin

    (Memorial Sloan Kettering Cancer Center)

  • Mark T. A. Donoghue

    (Marie-Josée and Henry R. Kravis Center for Molecular Oncology, Memorial Sloan Kettering Cancer Center)

  • William D. Tap

    (Memorial Sloan Kettering Cancer Center
    Weill Cornell Medical College)

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.

Suggested Citation

  • Sandra P. D’Angelo & Allison L. Richards & Anthony P. Conley & Hyung Jun Woo & Mark A. Dickson & Mrinal Gounder & Ciara Kelly & Mary Louise Keohan & Sujana Movva & Katherine Thornton & Evan Rosenbaum , 2022. "Pilot study of bempegaldesleukin in combination with nivolumab in patients with metastatic sarcoma," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-30874-8
    DOI: 10.1038/s41467-022-30874-8
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    1. Paul C. Tumeh & Christina L. Harview & Jennifer H. Yearley & I. Peter Shintaku & Emma J. M. Taylor & Lidia Robert & Bartosz Chmielowski & Marko Spasic & Gina Henry & Voicu Ciobanu & Alisha N. West & M, 2014. "PD-1 blockade induces responses by inhibiting adaptive immune resistance," Nature, Nature, vol. 515(7528), pages 568-571, November.
    2. Konrad J. Karczewski & Laurent C. Francioli & Grace Tiao & Beryl B. Cummings & Jessica Alföldi & Qingbo Wang & Ryan L. Collins & Kristen M. Laricchia & Andrea Ganna & Daniel P. Birnbaum & Laura D. Gau, 2020. "The mutational constraint spectrum quantified from variation in 141,456 humans," Nature, Nature, vol. 581(7809), pages 434-443, May.
    3. Friedman, Jerome H. & Hastie, Trevor & Tibshirani, Rob, 2010. "Regularization Paths for Generalized Linear Models via Coordinate Descent," Journal of Statistical Software, Foundation for Open Access Statistics, vol. 33(i01).
    4. Florent Petitprez & Aurélien Reyniès & Emily Z. Keung & Tom Wei-Wu Chen & Cheng-Ming Sun & Julien Calderaro & Yung-Ming Jeng & Li-Ping Hsiao & Laetitia Lacroix & Antoine Bougoüin & Marco Moreira & Gui, 2020. "B cells are associated with survival and immunotherapy response in sarcoma," Nature, Nature, vol. 577(7791), pages 556-560, January.
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