Phase IIa trial initiated for Descartes-11, a mRNA CAR T-cell therapy for patients with newly diagnosed, high-risk MM

Descartes-11, a mRNA chimeric antigen receptor (CAR) T-cell therapy, is moving into a phase IIa clinical trial for patients with newly diagnosed, high-risk multiple myeloma (MM).¹ Descartes-11 expresses CAR T-cell molecules transiently and therefore avoids some characteristic toxicities of these therapeutic agents. The phase IIa study (NCT04436029) aims to enroll 30 patients in a single-arm multicenter study in the US. This study will specifically enroll patients with MM who have residual disease after finishing induction therapy. The aim of this trial will be to examine the measurable residual disease-negative complete response following consolidation with Descartes-11.

A phase I study (NCT03994705) of 18 patients has already been undertaken, and results showed no evidence of cytokine release syndrome or neurotoxicity – adverse events commonly associated with CAR T-cell treatment. The efficacy of CAR T-cells is dependent on proliferation in vivo. However, as CAR expression is transient in Descartes-11, lymphodepletion preconditioning chemotherapy is not required with this treatment.

Preclinical data showed that cells engineered by transfection with an early non-humanized version of the agent (Descartes-08), expressed the anti-B-cell maturation antigen CAR for 1 week and were cytolytic in MM cells.² The magnitude of the response was correlated with the duration of CAR expression. Descartes-08 significantly increased survival in a mouse model (p < 0.001).