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PD-L1 blockade in combination with inhibition of MAPK oncogenic signaling in patients with advanced melanoma

Author

Listed:
  • Antoni Ribas

    (University of California Los Angeles (UCLA) and Jonsson Comprehensive Cancer Center at UCLA)

  • Alain Algazi

    (UCSF Medical Center)

  • Paolo A. Ascierto

    (Istituto Nazionale Tumori IRCCS Fondazione Pascale)

  • Marcus O. Butler

    (Princess Margaret Cancer Centre)

  • Sunandana Chandra

    (Northwestern Memorial Hospital)

  • Michael Gordon

    (HonorHealth Research Institute)

  • Leonel Hernandez-Aya

    (Washington University School of Medicine)

  • Donald Lawrence

    (Massachusetts General Hospital)

  • Jose Lutzky

    (Mount Sinai Medical Center)

  • Wilson H. Miller

    (Segal Cancer Center, Jewish General Hospital, Rossy Cancer Network, McGill University)

  • Katie M. Campbell

    (University of California Los Angeles (UCLA) and Jonsson Comprehensive Cancer Center at UCLA)

  • Bruno Delafont

    (AstraZeneca)

  • Shannon Marshall

    (AstraZeneca)

  • Nancy Mueller

    (AstraZeneca)

  • Caroline Robert

    (Gustave Roussy Cancer Campus and Paris-Saclay University)

Abstract

Combining PD-L1 blockade with inhibition of oncogenic mitogen-activated protein kinase (MAPK) signaling may result in long-lasting responses in patients with advanced melanoma. This phase 1, open-label, dose-escalation and -expansion study (NCT02027961) investigated safety, tolerability and preliminary efficacy of durvalumab (anti–PD-L1) combined with dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) for patients with BRAF-mutated melanoma (cohort A, n = 26), or durvalumab and trametinib given concomitantly (cohort B, n = 20) or sequentially (cohort C, n = 22) for patients with BRAF-wild type melanoma. Adverse events and treatment discontinuation rates were more common than previously reported for these agents given as monotherapy. Objective responses were observed in 69.2% (cohort A), 20.0% (cohort B) and 31.8% (cohort C) of patients, with evidence of improved tumor immune infiltration and durable responses in a subset of patients with available biopsy samples. In conclusion, combined MAPK inhibition and anti–PD-L1 therapy may provide treatment options for patients with advanced melanoma.

Suggested Citation

  • Antoni Ribas & Alain Algazi & Paolo A. Ascierto & Marcus O. Butler & Sunandana Chandra & Michael Gordon & Leonel Hernandez-Aya & Donald Lawrence & Jose Lutzky & Wilson H. Miller & Katie M. Campbell & , 2020. "PD-L1 blockade in combination with inhibition of MAPK oncogenic signaling in patients with advanced melanoma," Nature Communications, Nature, vol. 11(1), pages 1-10, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19810-w
    DOI: 10.1038/s41467-020-19810-w
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    Cited by:

    1. Jae Eun Choi & Yuanyuan Qiao & Ilona Kryczek & Jiali Yu & Jonathan Gurkan & Yi Bao & Mahnoor Gondal & Jean Ching-Yi Tien & Tomasz Maj & Sahr Yazdani & Abhijit Parolia & Houjun Xia & JiaJia Zhou & Shua, 2024. "PIKfyve, expressed by CD11c-positive cells, controls tumor immunity," Nature Communications, Nature, vol. 15(1), pages 1-15, December.

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