Dose Optimization of Mezigdomide is Key Element of SUCCESSOR-2 Trial

The SUCCESSOR-2 trial (NCT05552976) recently reported positive progression-free survival outcomes in patients with relapsed/refractory multiple myeloma who received mezigdomide, carfilzomib, and dexamethasone. During a discussion of his presentation at the Miami Cancer Institute’s Seventh Annual Immunotherapies Summit for Hematologic Malignancies of the SUCCESSOR clinical program, Paul G. Richardson, MD, director of Clinical Research and Clinical Program Leader at the Jerome Lipper Multiple Myeloma Center, the Dana-Farber Cancer Institute and RJ Corman Professor of Medicine, Harvard Medical School, highlighted the strategic importance of the phase 3 trial in addressing critical unmet needs within the multiple myeloma treatment landscape.

The trial focuses on a patient population who are refractory to CD38 monoclonal antibodies and lenalidomide, and who have experienced relapse after 1 to 3 prior lines of therapy. By targeting this specific group, the study aims to establish a new standard of care for patients whose previous treatments have failed them.

A defining feature of SUCCESSOR-2 is its dose optimization strategy. The trial was structured in 2 distinct stages. Stage 1 was a dose optimization phase designed to identify the most effective and tolerable dose and schedule, and stage 2 is a randomized phase 3 comparison utilizing the optimal dose established in the initial stage.

Richardson noted that this seamless approach is highly valuable because it provides researchers with a high level of confidence regarding the therapeutic dose and schedule before entering the randomized comparison. Furthermore, this methodology offers the FDA a clear, robust framework that may facilitate a more comfortable and streamlined approval process for the therapy.

The trial compares the addition of mezigdomide against a highly active carfilzomib and dexamethasone control regimen. Richardson expressed optimism that the results will clearly demonstrate the potential benefits of mezigdomide in this relapsed/refractory setting. By positioning mezigdomide as a potent oral agent, the SUCCESSOR-2 trial seeks to provide a convenient and effective backbone therapy for patients facing difficult-to-treat disease.