Safety and preliminary activity data from a single center phase II study of triplet combination of nivolumab (N) with dabrafenib (D) and trametinib (T) [trident] in patients (Pts) with BRAF-mutated metastatic melanoma (MM).

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Abstract
9560Background: Targeted therapies and immunotherapies (IMTs) have each improved survival for pts with BRAF V600 mutated MM, however many still progress and ultimately die from this disease. New combinatorial approaches targeting known mechanisms of resistance are needed. Preclinical data demonstrates that BRAF inhibition (BRAFi) in BRAF-mutated tumors is associated with increased T cell tumor infiltration and enhanced responses with combined BRAFi and PD-1 blockade in murine models, supporting the rationale for a clinical combinatorial approach. We hypothesize that N + DT is safe and will demonstrate clinical activity in BRAF-mutated pts with MM. Methods: We are conducting a phase II study (NCT02910700) of NDT in pts with BRAF-mutated unresectable stage III or IV MM. Prior PD-1 therapy is allowed but prior BRAFi/MEKi treatment is excluded. Pts with brain metastases are allowed if untreated and asymptomatic or mildly symptomatic/requiring stable or decreasing steroids (up to 4 mg PO dexamethasone). Pts re...