In preclinical studies. MOR202 mediated antibody-dependent cell-mediated cytotoxicity in MM cells derived from patients in vitro. Either Velcade® (bortezomib) or Revlimid® (lenalidomide) enhanced the cytotoxic activity of MOR202 in vitro and also the inhibition of MM-mediated bone lysis and tumor load in vivo. The enhancement by bortezomib was mediated through a direct cytotoxic effect on MM cells.
Lenalidomide synergistically enhanced MOR202 activity through several mechanisms identified as direct cytotoxicity, activation of effector cells and increased CD38 expression levels on MM cells. In an orthotopic xenograft murine model of multiple myeloma, MOR202 reduced tumor load and tumor-mediated bone lysis. Co-administration of MOR202 with either bortezomib or lenalidomide completely abolished bone lysis in a synergistic manner. These findings support further investigation of MOR202 combination regimens in clinical trials.