KappaMab

These data characterise the effects of LEN, DEX, and KM treatment on non-target immune cells in MM. Treatment may support destruction of MM cells by both direct action and indirect mechanisms via immune cells.

KappaMab (formerly MDX-1097) clinical trials have confirmed that normal leukocytes are not depleted by the antibody with no on-target off-tumour effects1-3, and preclinical KMA.CAR T cell data has confirmed the antibody specificity4. KMA or LMA are expressed on PCs at all stages of MM, and all plasmacytomas and AL patient samples. The increased Ag densities of both KMA and LMA compared to BCMA on RRMM BM PCs indicates antigen persistence on a treatment resistant clone. The combination of increased and persistent antigen density and the specificity of these therapeutic antibodies could provide a significant benefit in the treatment of myeloma and PCDs.1.

Chimeric Antigen Receptor (CAR)-T cell therapy has recently entered the standard of care for relapsed and refractory MM, following the recent FDA-approval of two CAR-T cell products, ide-cel® and cilta-cel®, which target the B cell maturation antigen (BCMA)...The monoclonal antibody, KappaMab (MDX-1097), binds to a conformational epitope on KMA, and has been assessed in phase I, IIa and IIb clinical trials in relapse refractory myeloma patients... Our data demonstrates that anti-KMA CAR-T cell therapy is a novel and potent treatment ready to enter a phase I clinical trial for patients with multiple myeloma.

Both single-agent KM and KM-Rd regimens were well tolerated, with the KM-Rd safety profile similar to patients given only Rd in other clinical settings. Based on the excellent safety profile and significant efficacy, further clinical trials escalating the KM dose and pairing KM with other standard-of-care treatments are planned.

Chimeric Antigen Receptor (CAR)-T cell therapy has recently entered the standard of care for relapsed and refractory MM, following the recent FDA-approval of two CAR-T cell products, ide-cel® and cilta-cel®, which target the B cell maturation antigen (BCMA)...The monoclonal antibody, KappaMab (MDX-1097), binds to a conformational epitope on KMA, and has been assessed in phase I, IIa and IIb clinical trials in relapse refractory myeloma patients (1)...We successfully generated human anti-KMA CAR-T cells with high and stable CAR expression and a predominately memory T cell phenotype...(1) Spencer et al. Blood Cancer Journal (2019) 9:58

KMA and LMA expression is independent of serum Ig and FLC levels and % marrow plasma cells. These data show that KappaMab and LambdaMab have therapeutic potential in the treatment of myeloma patients, especially in the setting of relapsed refractory disease where the combination of high antigen density and restriction of the target antigen to the malignant subpopulation of plasma cells will confer valuable clinical benefit.

Introduction: The novel kappa (κ) myeloma antigen (KMA) has been described and a specific monoclonal antibody KappaMab (formerly MDX-1097) developed which is currently in a Phase IIb clinical trial... These studies used mostly myeloma samples and a small number of other plasma cell dyscrasias. Nevertheless expression of KMA and LMA was identified on PCs across the spectrum of disease. Within the treated patient cohort the antigen density of KMA or LMA was higher than that of BCMA and implies there is an enrichment of these novel antigens in relapsed refractory myeloma.

We also performed droplet digital PCR (ddPCR) for exRNA transcripts of candidate biomarkers of lenalidomide (LEN) response in a “test cohort” of samples collected at study entry (baseline) and after five days of LEN treatment (C1D5) in a phase 1b trial of azacitidine in combination with LEN and dexamethasone (DEX) for patients with RR MM (ROAR trial; n= 24 patients). A “validation cohort” was obtained from a phase IIb trial of KappaMab in combination with LEN and DEX in RR MM (KappaMab trial; n=39 patients) at screening and C1D5... The data presented here provide the first demonstration of the utility of exRNA for biomarker identification and therapeutic monitoring. It provides the foundation for further exploration and development of exRNA testing as a potentially simple, non-invasive, repeatable strategy in MM.