Phase 1 Safety and Tolerability of MEDI4736 in Combination With Dabrafenib and Trametinib or With Trametinib Alone

A Phase 1 Open-label Study of Safety and Tolerability of MEDI4736 in Subjects With Metastatic or Unresectable Melanoma in Combination With Dabrafenib and Trametinib or With Trametinib Alone

The purpose of this study is to determine the maximum tolerated dose and characterize the safety profile of durvalumab (MEDI4736) in combination with dabrafenib and trametinib or with trametinib alone in participants with metastatic or unresectable melanoma with BRAF-mutation positive or wild-type (WT) BRAF, respectively.

This is a multicenter, open-label study with a dose escalation phase followed by an expansion phase of durvalumab administered in combination with dabrafenib and trametinib or with trametinib alone in participants with BRAF V600 mutation-positive and WT unresectable or metastatic melanoma, respectively.

Inclusion Criteria:

• Adults >= 18 years old
• Histologically confirmed cutaneous melanoma that is either Stage IIIc (unresectable) or Stage IV (metastatic) and determined to be BRAF V600E or V600K mutation-positive (cohort A) or mutation-negative (cohorts B and C)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Measurable disease by radiographic or physical examination
• Adequate organ and marrow function
• Willingness to provide consent for biopsies positive or BRAF WT measurable disease and adequate organ and marrow function

Exclusion Criteria:

• Prior treatment with a BRAF inhibitor or MEK inhibitor
• Any prior Grade >= 3 immune-related adverse event while receiving immunotherapy
• Active or prior documented autoimmune disease within the past 2 years
• History of or current risk for retinal vein occlusion (RVO) or central serous retinopathy (CSR)
• History of or current cardiovascular risk including myocardial infarction, >= Class II congestive heart failure, uncontrolled arrhythmias, or refractory hypertension
• Active, untreated central nervous system (CNS) metastases
• Women who are pregnant or lactating