Descartes-08 for Lupus

(SLE-001 Trial)

Overseen By Study Trial Central Mailbox

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Cartesian Therapeutics

Must be taking: Glucocorticoids, Immunosuppressives

Disqualifiers: Severe lupus nephritis, Severe CNS lupus, Major chronic illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial studies a new treatment called Descartes-08 for people with lupus, an autoimmune disease where the immune system attacks the body. The research aims to determine if Descartes-08 is safe, can be successfully produced, and helps reduce lupus symptoms. Descartes-08 involves modifying a person's own immune cells to better target the disease. People with active lupus symptoms, despite trying several treatments, might be suitable for this study. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important findings.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, since it mentions ongoing immunosuppressive therapy, you might be able to continue some medications. It's best to discuss this with the trial team.

Is there any evidence suggesting that Descartes-08 is likely to be safe for humans?

Research has shown that Descartes-08, a therapy using modified immune cells, has shown promise in earlier studies for treating conditions like lupus. In these studies, patients who received Descartes-08 experienced strong and lasting improvements, suggesting the treatment might be effective.

Although detailed safety information from these studies remains limited, the current phase of the trial indicates that earlier research has checked Descartes-08 for safety. Treatments reaching this stage have usually passed initial safety tests. Participants will be closely monitored for any side effects as more information is collected.

Overall, Descartes-08 appears to be a promising option, but participants should discuss any concerns with trial coordinators to fully understand the possible risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for lupus?

Unlike standard lupus treatments that often focus on managing symptoms with immunosuppressants or corticosteroids, Descartes-08 takes a novel approach by using autologous T-cells engineered to express a chimeric antigen receptor (CAR) targeting BCMA (B-cell maturation antigen). This means it harnesses the body's own immune cells to specifically target and potentially eliminate the problematic cells driving the disease. Researchers are excited because this targeted action could offer a more precise treatment with fewer side effects, potentially leading to better long-term outcomes for lupus patients.

What evidence suggests that Descartes-08 might be an effective treatment for lupus?

Research shows that Descartes-08, a new therapy using modified immune cells, may help treat lupus. This therapy assists patients with lupus nephritis, a type of kidney inflammation caused by lupus, by safely and effectively reducing symptoms and controlling the disease. Its potential success comes from targeting a protein called BCMA, linked to lupus activity. This method has effectively treated difficult cases of lupus nephritis, suggesting it might also help with other lupus symptoms. While more research is needed, these early results offer hope for those seeking new lupus treatments. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with systemic lupus erythematosus (SLE) who still have symptoms despite trying at least two immunosuppressive medications and steroids. They must also have specific autoantibodies present in their blood.

Inclusion Criteria

I have been diagnosed with systemic lupus erythematosus (SLE).

My blood test shows I have specific antibodies related to my condition.

I still have symptoms despite taking steroids and two other immune-suppressing drugs for 3 months.

Exclusion Criteria

Patient is pregnant or lactating

I do not have severe kidney or brain lupus, or major neurological symptoms from lupus.

Major chronic illness that is not well managed at the time of study entry and in the opinion of the investigator may increase the risk to the patient

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

8 weeks

Treatment

Participants receive Descartes-08 CAR T-cells to evaluate safety, tolerability, and manufacturing feasibility

8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Descartes-08

Trial Overview The study is testing the safety, how well patients can tolerate, and the production process of a CAR T-cell therapy called Descartes-08 in people with SLE to see if it's feasible as a treatment option.

How Is the Trial Designed?

Group I: Descartes-08 Experimental Treatment 1 Intervention

Drug: Descartes-08 Autologous T-cells expressing a chimeric antigen receptor directed to BCMA

Descartes-08 is already approved in United States for the following indications:

Approved in United States as Descartes-08 for:

• Generalized Myasthenia Gravis (MG)
• Systemic Lupus Erythematosus (SLE)
• Juvenile Dermatomyositis (JDM)

Who Is Running the Clinical Trial?

Cartesian Therapeutics

Lead Sponsor

Trials

10

Recruited

300+

Published Research Related to This Trial

A 56-year-old male with refractory isolated CNS-MM was treated with BCMA-CART therapy, which led to a partial response sustained for 5.5 months, indicating potential efficacy for this rare condition.

The treatment caused severe neurological complications, but these were reversible with intravenous methylprednisolone, highlighting the need for careful monitoring of side effects in BCMA-CART therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case Report: Reversible Neurotoxicity and a Clinical Response Induced by BCMA-Directed Chimeric Antigen Receptor T Cells Against Multiple Myeloma With Central Nervous System Involvement. Zhang, Y., Zhang, C., Zhou, J., et al.[2021]

Using CAR T cells to continuously deplete B cells leads to remission of lupus symptoms in mice that are genetically predisposed to the disease, suggesting a potential therapeutic strategy for lupus.

This study highlights the effectiveness of targeted cell therapy in managing autoimmune diseases, demonstrating that manipulating the immune system can result in significant health improvements.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Slamming the brakes on lupus with CAR T cells. Clark, RA.[2019]

The novel CD8+ CAR T-cell therapy, Descartes-08, shows promise for treating multiple myeloma by limiting the duration of CAR expression to one week, which helps prevent uncontrolled cell proliferation while maintaining effective cytolytic activity against myeloma cells.

In preclinical mouse models, Descartes-08 significantly inhibited myeloma growth and improved survival rates, and ongoing clinical trials are showing preliminary durable responses, paving the way for further testing in newly diagnosed patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of CD8+ anti-BCMA mRNA CAR T cells for treatment of multiple myeloma. Lin, L., Cho, SF., Xing, L., et al.[2021]

Recent advancements in CAR T cell therapy targeting CD19 have shown promising results in treating autoimmune diseases, leading to rapid and sustained depletion of autoreactive B cells.

Patients with refractory systemic lupus erythematosus and dermatomyositis experienced complete clinical and serological remission after treatment with autologous CD19 CAR T cells, highlighting a potential new approach for those who do not respond to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cell therapy in autoimmune diseases. Schett, G., Mackensen, A., Mougiakakos, D.[2023]

In a study of six patients with refractory systemic lupus erythematosus (SLE), anti-CD19 CAR T cell therapy was found to be well tolerated and led to a significant reduction in inflammatory cytokines IL-6 and TNFα three months after treatment.

The therapy also resulted in a marked decrease in SLE-associated antibodies in five out of six patients, suggesting a potential mechanism for its efficacy in managing SLE symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cytokine and reactivity profiles in SLE patients following anti-CD19 CART therapy. Nunez, D., Patel, D., Volkov, J., et al.[2023]

C-CAR088, a novel anti-BCMA CAR T-cell therapy, demonstrated a high overall response rate of 96.4% in patients with relapsed or refractory multiple myeloma, with significant rates of complete response (10.7%) and stringent complete response (46.4%).

The therapy showed a favorable safety profile, with 93.5% of patients experiencing cytokine release syndrome (CRS) that was manageable and reversible, and no dose-limiting toxicities reported across the tested dosages.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of C-CAR088, a novel humanized anti-BCMA CAR T-cell therapy in relapsed/refractory multiple myeloma. Qu, X., An, G., Sui, W., et al.[2022]

APRIL-CAR T cells showed rapid but not long-lasting antitumor responses in mouse models of multiple myeloma, indicating a need for improved strategies to sustain efficacy.

The study revealed that BCMA, the target antigen, was quickly downmodulated and internalized by myeloma cells after CAR T cell interaction, which may contribute to treatment resistance and tumor progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Both APRIL and antibody-fragment-based CAR T cells for myeloma induce BCMA downmodulation by trogocytosis and internalization. Camviel, N., Wolf, B., Croce, G., et al.[2022]

A new BCMA CAR-T cell therapy using the 4C8A monoclonal antibody showed strong and selective binding to BCMA, leading to effective targeting and destruction of multiple myeloma cells in vitro.

In mouse models, BCMA CAR-T cells significantly inhibited tumor formation and caused substantial shrinkage of established tumors, demonstrating their potential efficacy for treating multiple myeloma and supporting further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cells Based on Novel BCMA Monoclonal Antibody Block Multiple Myeloma Cell Growth. Berahovich, R., Zhou, H., Xu, S., et al.[2020]

BCMA-targeted CAR-T-cell therapy shows high efficacy in treating multiple myeloma, with an overall response rate of 80.5% and a complete response rate of 44.8% across 23 different CAR-T products studied in 640 patients.

Despite significant toxicity, including cytokine release syndrome in 80.3% of patients and neurotoxicity in 10.5%, the therapy offers a median progression-free survival of 12.2 months, which is substantially better than the expected 1.9 months for standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and clinical efficacy of BCMA CAR-T-cell therapy in multiple myeloma. Roex, G., Timmers, M., Wouters, K., et al.[2021]

CAR T therapy, known for its success in treating blood cancers, has been applied to systemic lupus erythematosus in a small study involving five patients, indicating its potential beyond cancer treatment.

The findings from Mackensen et al. suggest that CAR T therapy could be a promising new approach for autoimmune diseases, warranting further research in this area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T therapy extends its reach to autoimmune diseases. Baker, DJ., June, CH.[2023]

In a small study of five treatment-resistant patients with systemic lupus erythematosus (SLE), CD19 CAR T cell therapy led to significant clinical improvements and remission in all participants after 3 months, demonstrating its potential efficacy.

The treatment was well tolerated, with only mild cytokine release syndrome reported, suggesting a favorable safety profile for this innovative therapy in seriously ill SLE patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Journal Club: Anti-CD19 Chimeric Antigen Receptor T Cell Therapy for Refractory Systemic Lupus Erythematosus. Boulougoura, A., Gendelman, H., Surmachevska, N., et al.[2023]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40681435/

BCMA-targeted CAR T cell therapy can effectively induce ... Anti-BCMA CAR T therapy can help LN patients inducing and maintaining disease remission status safely and effectively.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06038474

Study Details | NCT06038474 | Descartes-08 for Patients ... This is a Phase II study to evaluate the safety, tolerability and manufacturing feasibility of Descartes-08 CAR T-cells in patients with Systematic Lupus ...

3. ir.cartesiantherapeutics.com ir.cartesiantherapeutics.com/news-releases/news-release-details/cartesian-therapeutics-reports-second-quarter-2025-financial

Cartesian Therapeutics Reports Second Quarter 2025 ... The randomized, double-blind, placebo-controlled Phase 3 AURORA trial is designed to assess Descartes-08, Cartesian's autologous anti-B cell ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S000349672504186X

BCMA-targeted CAR T cell therapy can effectively induce ... This study indicates that anti-BCMA strategy is potentially effective for CAR T cell based therapy in treating refractory LN.

5. ir.cartesiantherapeutics.com ir.cartesiantherapeutics.com/news-releases/news-release-details/cartesian-therapeutics-highlights-progress-and-2025-strategic

Release Details Descartes-08, Cartesian's lead mRNA cell therapy candidate, is an autologous mRNA-engineered chimeric antigen receptor T-cell therapy (mRNA CAR- ...

6. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/443999

Descartes-08 for Patients With Systemic Lupus Erythematosus This is a Phase II study to evaluate the safety, tolerability and manufacturing feasibility of Descartes-08 CAR T-cells in patients with Systematic Lupus ...

7. ir.cartesiantherapeutics.com ir.cartesiantherapeutics.com/news-releases/news-release-details/cartesian-therapeutics-descartes-08-observed-provide-deep-and

Cartesian Therapeutics' Descartes-08 Observed to Provide ... Descartes-08-treated participants were observed to sustain deep responses through long-term follow-up, with an average 4.8-point reduction in MG-ADL at Month ...