Cobimetinib-based treatment for R/R multiple myeloma

Marc Raab, MD, German Cancer Research Center, Heidelberg, Germany, shares the details of a Phase Ib/II study (NCT03312530) of the MEK inhibitor cobimetinib (C) to treat relapsed/refractory (R/R) multiple myeloma as a single agent or combined with venetoclax (V) and atezolizumab (A). Cobimetinib was theorized to be more efficacious in combination with BCL-2 inhibition and PD-L1 inhibition due to a shift in apoptotic balance towards death and an improved anti-tumor immune response. Patients were randomized across three arms: C, C+V, or C+V+A and responses and pharmacokinetics were analyzed. The results found that responses were significantly higher in the two combination treatment groups for t(11;14) positive patients compared to non-t(11;14). Since efficacy was poor in the single agent arm and addition of A to C+V did not significantly improve outcomes, further investigation will continue into C+V treatment for t(11;14) positive patients. This interview took place during the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition, 2020.