Novel BCMA Targeted ADCs, Bispecific and Trispecific Antibodies

Abstract

Over the past five years, several antibody-based therapeutic approaches have been investigated in multiple myeloma (MM) beyond the naked antibodies that had targeted DKK1, CD38 and SLAMF7. The antibody-drug conjugates (ADCs) have been utilized for different solid and hematologic malignancies to deliver a toxic payload to a cancer cells with a specific surface marker. Belantamab mafodotin (Belamaf) is the first FDA approved, B-cell maturation antigen (BCMA) targeting ADC in triple-class exposed, relapsed and/or refractory MM beyond four prior lines of therapy. Belamaf is now being combined with other drug classes in earlier lines of therapy. There are other MM surface markers beyond BCMA being targeted with ADCs (CD38, CD46, CD56, CD74, CD138, etc.) but are in early clinical development. Bispecific antibodies (BsAbs) were conceived as a novel idea to direct the cytotoxic immune effector cells system towards cancer cells in the late 1960s but came to fruition clinically in the 2000s. The initial wave of BsAbs recognize CD3 on the T-cells whereas the MM specific surface markers that have been targeted include BCMA, GPRC5D, CD38, FCRH5 (Table 1). Although there are BsAbs in preclinical development exploring CD16 in place of CD3 to help direct natural killer cells towards the tumor cells, the present talk will summarize clinical data on BsAbs in MM that have been reported at recent international congresses. Lastly, the trispecific antibodies are in preclinical development with dual MM surface markers targeting in an attempt to increase MM cell specificity.