OCEAN: A Phase 3, Randomized, Global Study of Melflufen and Dexamethasone Versus Pomalidomide and Dexamethasone in Patients With Relapsed/Refractory Multiple Myeloma Refractory to Lenalidomide

Purpose of the Study: Only 20%-30% of patients with relapsed/ refractory multiple myeloma (RRMM) respond to the next line of treatment, and ultimately most will relapse. Melflufen is a lipophilic peptide-conjugated alkylator that rapidly delivers a highly cytotoxic payload into myeloma cells through peptidase activity. Aminopepti- dases are expressed in cancer cells and are key to the transformation process in multiple myeloma (MM). Melflufen targets MM with 50-fold higher potency than melphalan (Chauhan et al. Clin Cancer Res. 2013). In the phase 1/2 study O-12-M1 of patients with RRMM and 2 prior lines of therapy, including lenalidomide and bortezomib, melflufen and dexamethasone (dex) showed promising activity with an overall response rate (ORR) of 31%, median progression-free sur- vival (PFS) of 5.7 months, and median overall survival (OS) of 20.7 months, as well as an acceptable safety profile (Richardson et al. Blood. 2017; Abstract 3150). OCEAN is evaluating melflufen-dex ver- sus pomalidomide-dex in a RRMM patient population comparable to that of the pivotal phase 3 pomalidomide trial MM-003.

Summarized Description of the Project: OCEAN (NCT03151811) is a global, phase 3, randomized, open-label study of melflufen-dex versus pomalidomide-dex in patients with RRMM who are refractory to the last-line of therapy and to lenalidomide within 18 months of randomi- zation. Planned enrollment is 450 patients. Patients must have mea- surable disease and 2 to 4 prior lines of therapy, including lenalidomide and a proteasome inhibitor. Exclusion criteria include prior pomalidomide, intolerance to IMiDs, and prior allogeneic stem cell transplantation with active graft-versus-host-disease. Patients are randomized 1:1 to receive either melflufen 40 mg intravenously on day 1 or pomalidomide 4 mg orally daily on days 1 to 21 of each 28-day cycle. Dexamethasone 40 mg will be administered on days  1, 8, 15, and 22 of each 28-day cycle for both regimens. The starting dexamethasone dose will be reduced to 20 mg in patients 75 years of age. Patients will be treated until disease progression or unacceptable toxicity. The primary endpoint is PFS assessed by Independent Review Committee per International Myeloma Working Group Uni- form Response Criteria. Key secondary endpoints include ORR, dura- tion of response, OS, and safety. The Data Safety Monitoring Committee reviewed the study in April 2019, and enrollment is ongoing.