Autologous Chimeric Antigen Receptor (CAR) T-cells Targeting the Kappa Myeloma Antigen (KMA) in Kappa Restricted Multiple Myeloma Patients With Relapsed/Refractory Disease

Summary

The study proposed here intends to evaluate the safety and efficacy of escalating doses of autologous PMCC-COE-KMA CAR T-cells administered to patients with relapsed/refractory multiple myeloma that expresses the KMA. The PMCC-COE-KMA CAR T-cells will be produced using LV and administered to patients after lymphodepleting conditioning chemotherapy. Considering the poor prognosis of myeloma patients who have relapsed after ≥ 2 lines of therapy, combined with evidence of PMCC-COE-KMA CAR T-cell specificity, as well as the efficacy and manageable toxicity of PMCC-COE-KMA, investigators believe the potential benefits outweigh the risks of this trial.

Timeline

Start

2026-05

Primary completion

2028-09

Completion

2030-01

Publications

• Background 1. Ramos, C.A., et al., Clinical responses with T lymphocytes targeting malignancyassociated kappa light chains. J Clin Invest, 2016. 126(7): p. 2588-96. Boux, H.A., et al., A tumor-associated antigen specific for human kappa myeloma cells. J Exp Med, 1983. 158(5): p. 1769-74. Boux, H.A., et al., The surface expression of a tumor-associated antigen on human kappa myeloma cells. Eur J Immunol, 1984. 14(3): p. 216-22. Goodnow, C.C. and R.L. Raison, Structural analysis of the myeloma-associated membrane antigen KMA. J Immunol, 1985. 135(2): p. 1276-80. Hutchinson, A.T., et al., Free Ig light chains interact with sphingomyelin and are found on the surface of myeloma plasma cells in an aggregated form. J Immunol, 2010. 185(7): p. 4179-88. Asvadi, P., et al., MDX-1097 induces antibody-dependent cellular cytotoxicity against kappa multiple myeloma cells and its activity is augmented by lenalidomide. Br J Haematol, 2015. 169(3): p. 333-43. Walker, K.Z., et al., A monoclonal antibody with selectivity for human kappa myeloma and lymphoma cells which has potential as a therapeutic agent. Adv Exp Med Biol, 1985. 186: p. 833-41. Dunn, R., et al., Phase 2a, open-label, multi-dose study of anti-kappa monoclonal antibody, MDX-1097, in relapsed kappa-chain restricted multiple myeloma with stable measurable disease. Haematologica Latina, 2013. 98(s1): p. 776. Spencer, A., et al., A phase I study of the anti-kappa monoclonal antibody, MDX-1097, in previously treated multiple myeloma patients. J Clin Oncol, 2010. 28: p. (suppl; abstract 8143). Spencer, A., et al., A phase I study of the anti-kappa monoclonal antibody, MDX-1097, in previously treated multiple myeloma patients. 2010. Gowrishankar, K., et al., Abstract 3572: CAR T-cells targeting the kappa myeloma antigen for the treatment of multiple myeloma. 2018. 78(13 Supplement): p. 35723572. Rejeski, K., et al., Immune effector cell-associated hematotoxicity: EHA/EBMT consensus grading and bes

Drugs

Indications