A phase 1/2 study of durvalumab (DURVA) in combination with lenalidomide (LEN) with or without dexamethasone (DEX) in patients (pts) with newly diagnosed multiple myeloma (NDMM).
TPS8055 Background: LEN + DEX (Rd) is approved for pts with newly diagnosed MM, including those who are transplant non-eligible (TNE). DURVA is a monoclonal antibody to programmed death ligand 1 (PD-L1) that blocks PD-L1 binding to programmed death-1 (PD-1). Preclinical studies showed anti-MM immune responses with PD-1/PD-L1 blockade that were enhanced with LEN (Görgün et al, 2015). Here, we present a phase 1/2, multicenter, open-label trial in progress (MEDI4736-MM-002) designed to evaluate DURVA in combination with LEN ± DEX in a target population of pts who are TNE and/or with high-risk NDMM. Methods: Enrollment of up to 138 pts from the US, Canada, and Europe is planned to determine the recommended dose of DURVA (primary endpoint) with LEN ± DEX for the treatment (Tx) of NDMM. Key secondary endpoints include safety, response outcomes, pharmacokinetics, progression-free survival, and overall survival. Pts with previously untreated MM with ≥ 1 of the following will be included: 1 of the CRAB criteria or clonal bone marrow plasma cells ≥ 60% and an Eastern Cooperative Oncology Group performance status of ≤ 2. Pts with a history of primary immunodeficiency will be excluded. Each independent cohort (A, B, C) will enroll 6 pts in parallel in the dose-finding phase (Table). Dose-limiting toxicities will be evaluated during the first cycle of Tx. The optimal regimen will be determined from the dose-finding phase and a parallel dose-expansion phase of up to 40 pts per cohort. Tx will continue until progressive disease or unacceptable toxicity. To date, 15 pts have enrolled. Clinical trial information: NCT02685826. [Table: see text]