EXCALIBER-RRMM: a phase III trial of iberdomide, daratumumab, and dexamethasone in relapsed/refractory multiple myeloma.

Multiple myeloma (MM) is a plasma cell neoplasm that stems from the malignant transformation of clonal plasma cells. It is characterized by multiple periods of remission and relapse requiring multiple lines of therapy, with response to treatment and survival decreasing with each successive relapse. To achieve deep and durable responses in relapsed/refractory MM (RRMM), novel treatments are required. Iberdomide (IBER), an oral CELMoD™ agent, is associated with greater tumoricidal and immune-stimulatory effects than immunomodulatory drugs (IMiDs®). IBER has been shown to have synergy with dexamethasone (DEX) and daratumumab (DARA) in vitro. In a phase I/II trial, IBER in combination with DARA and DEX (IberDd) was well tolerated and demonstrated promising preliminary efficacy in patients with heavily pretreated RRMM, including patients refractory to IMiD agents, DARA, and proteasome inhibitors. EXCALIBER-RRMM is a unique confirmatory phase III trial that incorporates a 2-stage seamless design to firstly address dose optimization of IberDd, and secondly, to compare the efficacy and safety of the selected IberDd dose with DARA, bortezomib, and DEX in patients with early-line (1 or 2 prior lines of therapy) RRMM. www.clinicaltrials.gov identifier is NCT04975997.