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Also known as Decartes-08, Descartes 11
Descartes-08 · 6 trials · 9 indications
To evaluate the efficacy of Descartes-08 as assessed by the proportion of Myasthenia Gravis Activities of Daily Living (MG-ADL) responders at Month 4.
Proportion of participants in the Descartes-08 group compared with placebo who achieve major improvement marked by ≥60 point improvement on the 2016 ACR/EULAR Total Improvement Score (TIS)
Results will be descriptive. Safety and tolerability endpoints will include descriptive statistics of AEs and SAEs. Patients must be followed until all AEs have resolved to Grade 2 or less except for lymphopenia and alopecia.
Per IMWG 2016 Response Criteria Summary sCR: Complete response (CR) plus a normal free light chain ratio and no clonal cells in bone marrow (by immunohistochemistry). The FLC ratio must be Kappa/Lambda ≤ 4:1 or ≥ 1:2 after counting at least 100 plasma cells. CR: Negative immunofixation in serum and urine, disappearance of any soft tissue plasmacytomas, and \<5% plasma cells in bone marrow. VGPR: Serum M-protein detectable by immunofixation (not on electrophoresis) or a ≥ 90% reduction in M-protein, with urine M-protein \<100 mg/24 hours. PR: ≥ 50% reduction in serum M-protein and a ≥ 90% reduction in 24-hour urinary M-protein (or to \<200 mg/24 hours). If M-protein is unmeasurable, a ≥ 50% decrease in the difference between involved and uninvolved FLC levels is required. If both M-protein and serum-free light chains are unmeasurable, a ≥ 50% reduction in plasma cells is necessary, provided baseline plasma-cell percentage in bone marrow was ≥ 30%. Overall Response (OR): CR+VGPR+PR
In Part 3, the primary objective is to compare the effect of Descartes-08 versus placebo, as measured by the change in MGC score from baseline to Week 12. In Part 1, up to three ascending doses of Descartes-08 will be administered to each of 3 to 6 patients; the patients will be staggered at least 21 days apart and will complete a safety review between each dose. In Part 2, patients will receive up to 6 doses in three different schedules depending on the arm they were enrolled into and will be monitored for up to 1 year to assess the safety and tolerability of a repeated dosing schedule.
The primary endpoint for Part-1 is the Maximum Tolerated Dose (MTD), defined as the Dose Level at which no more than 20% of the patients treated have shown Dose-Limiting Toxicity (DLT), i.e. at which 3 patients received all 6 weekly infusions without a DLT by Day 50; or 6 patients received 3 weekly infusions with no more than 1 patient having a DLT by Day 50. The primary endpoint for Part-2 is the type and frequency of treatment-related SAEs. This will be assessed on Days 22, 50 and Months 3,6,9,12
The primary endpoint for Part-1 is the Maximum Tolerated Dose (MTD), defined as the Dose Level at which no more than 20% of the patients treated have shown Dose-Limiting Toxicity (DLT), i.e. at which 3 patients received all 6 weekly infusions without a DLT by Day 50; or 6 patients received 3 weekly infusions with no more than 1 patient having a DLT by Day 50. The primary endpoint for Part-2 is the type and frequency of treatment-related SAEs.
| Arm | Type | Description |
|---|---|---|
| Decartes-08 | EXPERIMENTAL | This group will undergo leukapheresis and receive manufactured Decartes-08 |
| Placebo | PLACEBO_COMPARATOR | This group will receive placebo |
| Descartes-08 | OTHER | Drug: Descartes-08 Autologous T-cells expressing a chimeric antigen receptor directed to BCMA |
| Descartes 11 | EXPERIMENTAL | - |
| Phase 1b Dose-Escalation | EXPERIMENTAL | Generalized Myasthenia Gravis |
| Phase IIa Expansion | EXPERIMENTAL | Generalized Myasthenia Gravis |
| Phase IIb Randomized Control Trial | PLACEBO_COMPARATOR | Generalized Myasthenia Gravis |
| Part 1: Decartes-08 to establish Maximum tolerated dose | EXPERIMENTAL | Intra-patient dose escalation arm with three dose levels over the course of six infusions of cell product. |
| Part 2: Decartes-08 infusions once weekly for 6 weeks | EXPERIMENTAL | Descartes-08 infusions at the maximum tolerated dose level from Part 1. |
| Name | Type | Description |
|---|---|---|
| Decartes-08 | BIOLOGICAL | Autologous mRNA CAR T-cell therapy |
| Placebo Drug | OTHER | infusion without Decartes-08 |
| Descartes-08 | DRUG | Autologous T-cells expressing a chimeric antigen receptor (CAR) directed to B-Cell maturation antigen (BCMA) |
| Placebo | OTHER | Plasma-Lyte |
| Descartes 11 | BIOLOGICAL | Car T-cells |
Inclusion Criteria: * Patient must be at least 18 years of age. * Patient must have generalized myasthenia gravis (gMG), Myasthenia Gravis Foundation of America (MGFA) clinical classification grades 2-4 at the time of Sscreening. * MG-Activities of Daily Living (MG ADL) total score ≥ 6. * Concomita...
Descartes-08 is an investigational cell therapy being studied in autoimmune and inflammatory conditions, including antisynthetase syndrome, childhood-onset systemic lupus erythematosus, generalized myasthenia gravis, and systemic lupus erythematosus. It is also being evaluated in multiple myeloma. It has not been approved for any indication and remains in clinical development.
Descartes-08 targets BCMA, or B-cell maturation antigen. BCMA is a protein expressed on antibody-producing plasma cells and certain B cells, and targeting it is intended to deplete the cells that drive autoantibody-mediated autoimmune disease. Descartes-08 is described as an mRNA CAR T-cell therapy directed at BCMA.
Descartes-08 is developed by Cartesian Therapeutics, Inc., which trades on the Nasdaq under the ticker RNAC. The company is running the clinical program for the asset across autoimmune indications and multiple myeloma.
Descartes-08 is in Phase 2 development overall, with individual studies spanning Phase 1 through Phase 3. A Phase 3 trial in myasthenia gravis is active but no longer recruiting, while Phase 2 and Phase 1 studies in other autoimmune conditions are currently recruiting. It is investigational and has not been approved.
Descartes-08 is being studied in several registered trials. NCT06799247 is a Phase 3 study in myasthenia gravis across the United States, Canada, Italy, Poland, Serbia, Spain, Turkey, and the United Kingdom. NCT07391605 is a Phase 2 trial in antisynthetase syndrome, NCT07089121 is a Phase 1 study in children and young adults with autoimmune disorders, and NCT06038474 is a Phase 2 study in systemic lupus erythematosus.
Yes. Descartes-08 is also written as Decartes-08 and Descartes 11. These are alternate spellings and names for the same investigational BCMA-targeted mRNA CAR T-cell therapy developed by Cartesian Therapeutics, Inc. (RNAC).