Cartesian Therapeutics Doses First Patient With mRNA CAR-T Descartes-15 in Trial for R/R Multiple Myeloma

Cartesian Therapeutics has dosed the first patient with Descartes-15, an investigational next-generation autologous mRNA-engineered chimeric antigen receptor T-cell therapy (CAR-T) therapy that targets B-cell maturation antigen (BCMA), in a phase 1 clinical trial (NCT06304636) evaluating the product for the treatment of relapsed/refractory (r/r) multiple myeloma (MM).¹

According to Cartesian, Descartes-15 includes technology intended to provide it with predictable and controllable pharmacokinetics and enhanced CAR stability. Notably, the cell therapy, which does not use integrating vectors, is also intended to be delivered to patients in an outpatient setting without the need for conditioning chemotherapy. Cartesian additionally pointed out that in preclinical research Descartes-15 has exhibited a 10-fold superiority in CAR expression and selective target-specific killing compared to Descartes-08, the company’s lead product candidate, which is an autologous, BCMA-directed, mRNA-engineered CAR-T therapy currently under evaluation for the treatment of autoimmune indications including myasthenia gravis (MG) and systemic lupus erythematosus.^1,2

The first-in-human phase 1 trial for Descartes-15, which is primarily focused on safety and tolerability, takes the form of a dose escalation study. According to the clinicaltrials.gov page, the trial is open to patients with r/r MM aged 18 years and older who have previously been treated unsuccessfully with at least 3 prior lines of therapy, including an immunomodulatory drug, a proteasome inhibitor, and an antiCD38 drug or biologic; only 1 study site in Bethesda, Maryland is currently listed. Although the trial includes plans to treat patients without prior lymphodepletion in a later part of the study, the initial patients will receive lymphodepletion before treatment with the CAR-T. Pending the results of the trial, Cartesian plans to eventually evaluate Descartes-15 for the treatment of autoimmune diseases.

“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,” Carsten Brunn, PhD, the president and chief executive officer of Cartesian Therapeutics, said in a statement.¹ “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.”

In July 2024, Cartesian Therapeutics reported data from the phase 2b portion of a clinical trial (NCT04146051) evaluating Descartes-08 for MG that is using MG Composite (MGC) score as a primary end point.³ 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 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).

CGTLive® previously spoke to Miloš Miljković, MD, the chief medical officer of Cartesian Therapeutics, at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, Maryland. He spoke about the cell therapy and its potential in treating MG with regard to the data from the trial that had been reported as of that time.⁴

“mRNA cell therapy seems to be very clinically active in autoimmune diseases,” Miljković told CGTLive in the interview. “MG is the lead indication. It's administered without lymphodepletion chemotherapy and in an outpatient setting and has a great safety profile with no cytokine release syndrome, no neurotoxicity or immune effector cell-associated neurotoxicity syndrome, and no dose limiting toxicities across all patients who were treated under open label.”

REFERENCES
1. Cartesian Therapeutics announces first patient dosed in first-in-human phase 1 trial of next-generation mRNA CAR-T cell therapy Descartes-15. News release. September 3, 2024. Accessed September 6, 2024. https://ir.cartesiantherapeutics.com/news-releases/news-release-details/cartesian-therapeutics-announces-first-patient-dosed-first-human
2. Cartesian Therapeutics receives FDA regenerative medicine advanced therapy (RMAT) designation for Descartes-08 for the treatment of myasthenia gravis. News release. Cartesian Therapeutics, Inc. May 22, 2024. Accessed May 24, 2024. https://ir.cartesiantherapeutics.com/news-releases/news-release-details/cartesian-therapeutics-receives-fda-regenerative-medicine
3. Cartesian Therapeutics announces positive topline results from phase 2b trial of Descartes-08 in patients with myasthenia gravis. News release. Cartesian Therapeutics, Inc. July 2, 2024. Accessed July 2, 2024. https://ir.cartesiantherapeutics.com/news-releases/news-release-details/cartesian-therapeutics-announces-positive-topline-results-phase
4. Howard JF, Mozaffar T, Vu T, et al. Investigation of mRNACellTherapy as a Treatment for AutoimmuneDisease in Patients withMyastenia Gravis. Presented at: ASGCT 27th Annual Meeting, May 7-10; Baltimore, Maryland. Abstract #241