mRNA-Based CAR T-Cell Therapy Descartes-11 Moves Into Phase 2 Trial in Myeloma

A phase 2 clinical trial (NCT04436029) has been initiated to evaluate Descartes-11, an mRNA CAR T-cell therapy, as a consolidative therapy in patients with newly diagnosed, high-risk multiple myeloma who have residual disease after induction therapy.¹

To date, Descartes-11 is the first RNA-engineered cellular therapy to enter clinical development for the frontline treatment of cancer, according to Cartesian Therapeutics, the engineer of the product.

“Patients [who are] newly diagnosed with high-risk multiple myeloma seldom achieve deep, durable responses after frontline therapy,” said Kenneth C. Anderson, MD, the Kraft Family Professor of Medicine at Harvard Medical School and program director of the Jerome Lipper Multiple Myeloma Center and LeBow Institute for Myeloma Therapeutics at Dana-Farber Cancer Institute, a 2014 Giant of Cancer Care® winner in Multiple Myeloma. “Integrating a CAR T-cell therapy into our standard of care, without using lymphodepleting chemotherapy, would be a welcome addition to our toolkit for treating this currently incurable disease.”

Multiple myeloma represents the second most common hematologic malignancy in the world and remains difficult to treat despite numerous therapeutic advances and drug approvals. Patients continue to experience multiple relapses and complications from the disease, affecting many areas of the body, such as the bones, kidneys, and immune system.

Descartes-11 is part of Cartesian Therapeutics RNA Armory^SM, a cellular therapy platform that “enables mRNA-engineering any cell, to target to any tissue, any combination of therapies.”² The platform utilizes autologous and allogeneic approaches to engineer products that optimize each therapy to different cell types. Moreover, the “army” of cells that is engineered deliver precision-targeted treatment directly to the myeloma cells with a defined half-life, which allows for repeat dosing and outpatient administration of some therapies.

The investigational Descartes-11 product is manufactured to express CAR molecules transiently rather than permanently, which could reduce some of the short- and long-term risks associated with traditional autologous CAR T-cell therapies.¹

Notably, the full therapeutic dose of Descartes-11 can be administered with each infusion as billions of cells are mRNA-engineered with the CAR molecule. Moreover, this eliminates the need for preconditioning, lymphodepleting chemotherapy that current CAR T-cell therapies require.

Phase 1 data showed no evidence of cytokine release syndrome or neurotoxicity with Decartes-11 in patients with advanced multiple myeloma. Currently, the emergence of these adverse effects remains a key challenge faced with CAR T-cell therapies in hematologic malignancies.

The open-label, phase 2 trial has a planned enrollment of approximately 30 patients with newly diagnosed multiple myeloma who remain minimal residual disease positive after completing a pre-transplant, anti-myeloma combination regimen comprised of a minimum of 2 drugs. Eligible patients must be 18 years or older at the time of enrollment.³

Those who are pregnant or lactating or those with active and uncontrolled infections are ineligible for enrollment.

The primary end point will be the 2-year stringent complete response rate.

The estimated primary completion date is set for April 2022, with an estimated study completion date set for April 2025.

References

1. Cartesian Therapeutics initiates phase 2 clinical trial of first RNA-engineered cell therapy for frontline cancer. Cartesian Therapeutics. News release. Published February 22, 2021. Accessed February 25, 2021. http://bit.ly/3pSNKBu.
2. RNA Armory. Cartesian Therapeutics. 2021. Accessed February 25, 2021. https://www.cartesiantherapeutics.com/rna-armory/.
3. Descartes-11 consolidation treatment in patients with high-risk multiple myeloma who have residual disease after induction therapy. ClinicalTrials.gov. Posted June 17, 2020. Updated February 10, 2021. Accessed February 25, 2021. https://clinicaltrials.gov/ct2/show/NCT04436029.