Skip to main content
eScholarship
Open Access Publications from the University of California

UCLA

UCLA Previously Published Works bannerUCLA

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

  • Author(s): Ribas, Antoni;
  • Algazi, Alain;
  • Ascierto, Paolo A;
  • Butler, Marcus O;
  • Chandra, Sunandana;
  • Gordon, Michael;
  • Hernandez-Aya, Leonel;
  • Lawrence, Donald;
  • Lutzky, Jose;
  • Miller, Wilson H;
  • Campbell, Katie M;
  • Delafont, Bruno;
  • Marshall, Shannon;
  • Mueller, Nancy;
  • Robert, Caroline
  • et al.
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.

Many UC-authored scholarly publications are freely available on this site because of the UC's open access policies. Let us know how this access is important for you.

Main Content
For improved accessibility of PDF content, download the file to your device.
Current View