Cartesian Therapeutics has dosed the first patient in a phase 1 clinical trial evaluating Descartes-15, an investigational next-generation autologous mRNA-engineered chimeric antigen receptor T-cell therapy (CAR-T), for the treatment of relapsed/refractory (r/r) multiple myeloma (MM). Descartes-15 targets B-cell maturation antigen (BCMA). The Phase 1 trial is identified as NCT06304636.
Novel mRNA CAR-T Design
Descartes-15 incorporates technology designed to provide predictable and controllable pharmacokinetics and enhanced CAR stability. Unlike traditional CAR-T therapies, Descartes-15 does not use integrating vectors and is intended for outpatient delivery without the need for conditioning chemotherapy. Preclinical research indicates that Descartes-15 exhibits a 10-fold superiority in CAR expression and selective target-specific killing compared to Descartes-08, Cartesian’s lead product candidate. Descartes-08 is currently under evaluation for autoimmune indications such as myasthenia gravis (MG) and systemic lupus erythematosus.
Phase 1 Trial Details
The first-in-human phase 1 trial is a dose escalation study primarily focused on safety and tolerability. The trial is enrolling patients aged 18 years and older with r/r MM who have previously been treated unsuccessfully with at least three prior lines of therapy, including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 drug or biologic. The initial patients will receive lymphodepletion before treatment with Descartes-15, though later stages of the trial may explore treatment without prior lymphodepletion. The trial is currently enrolling at a single site in Bethesda, Maryland.
Company Perspective
"Advancement of Descartes-15 into the clinic marks an important step forward in our mission to deliver innovative mRNA cell therapies to patients with autoimmune diseases," said Carsten Brunn, PhD, president and chief executive officer of Cartesian Therapeutics. "We believe that Descartes-15, which was designed leveraging our novel mRNA platform, could serve as a highly potent next-generation cell therapy with the ability to be dosed in the outpatient setting without preconditioning chemotherapy. We look forward to advancing this important program into development for autoimmune indications with high unmet need."
Descartes-08 Data in Myasthenia Gravis
In July 2024, Cartesian Therapeutics reported data from the phase 2b portion of a clinical trial evaluating Descartes-08 for MG. At 3 months posttreatment, 10 of 14 patients (71%) in the modified intent-to-treat (mITT) group, all of whom received at least 1 dose of Descartes-08, achieved a 5-point or greater improvement in MG Composite (MGC) score. In comparison, only 3 of 12 patients (25%) who received the placebo in the mITT showed a 5-point or greater improvement in MGC score (P = .018).
