Phase 1 study of MEDI4736, an anti-PD-L1 antibody, in combination with dabrafenib and trametinib or trametinib alone in patients with unresectable or metastatic melanoma.

TPS9108 Background: Greater understanding of tumor immunology in melanoma has led to the development of targeted treatments with improved outcomes in patients (pts) with metastatic melanoma (MM). Dabrafenib, a V600E BRAF inhibitor, combined with trametinib, a MEK inhibitor, resulted in high response rates, progression-free survival (PFS) of 9.4 mo in BRAF mutation-positive melanoma and is now an FDA-approved combination. Adding an immunomodulator may further improve outcomes. MEDI4736, a highly potent anti-PD-L1 antibody, showed clinical activity in a phase 1 study of pts with solid tumors including MM and is being evaluated in combination with dabrafenib/trametinib or trametinib alone in BRAF mutation-positive or BRAFmutation-negative melanoma. Methods: This global, multicenter, open-label phase 1b study (NCT02027961) is enrolling adults with unresectable or MM and ECOG performance status 0-1 into 3 cohorts. In cohort A, BRAF V600E or V600K mutation-positive (BRAF-MP) pts receive dabrafenib orally (PO) t...