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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.
Published Web Location
https://doi.org/10.1038/s41467-020-19810-wAbstract
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.
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