A Phase IIb, open label, sequential cohort study comparing KappaMab alone to KappaMab in combination with lenalidomide and low dose dexamethasone [MRd] in Relapsed Refractory Multiple Myeloma (ACTRN12616001164482)

This study builds upon pre-clinical and early-phase studies of KappaMab, a chimeric IgG1 mAb specific for KMA (3). Importantly, to date, KMA represents the only truly MM-specific mAb under clinical development. KMA is a tumour-specific cell surface antigen that is (unlike CD38, SLAMF7 or CD138) exclusively expressed on MM cells, including stem-like CD138-ve/CD45+ve populations. KappaMab binds to a unique conformational epitope on KMA which is presented on the myeloma cell membrane by kappa FLC (?FLC) that is not associated with immunoglobulin heavy chain. Furthermore, KappaMab shows a 5-fold higher avidity for membrane-bound KMA (IC50 2nM) over secreted kappa free light chains (FLC), consistent with no sink effect being demonstrable in the presently completed early phase clinical trials. In vitro studies show selective engagement of ADCC and antibody dependent cell phagocytosis by KappaMab on kappa-positive MM cells, moreover, LEN treatment upregulates KMA expression on MM cells promoting enhanced NK-mediated ADCC. This therefore provides a strong rationale for combining KappaMab with IMiDs, due to concurrent upregulation of the KMA target and effector cell cytotoxicity.

Trial phase

Phase 2

Trial participation type

This trial has been designed for the Clinical Research of a Drug.

Principal investigator

Prof Andrew Spencer

Key inclusion data

Relapsed and/or refractory kappa restricted MM (Appendix 3); Received 1-3 prior lines of therapy; Induction + ASCT + maintenance = 1 line of therapy; No prior lenalidomide therapy.