SYNCAR-001 + STK-009 for Lupus

Not currently recruiting at 4 trial locations

Overseen By Clinical Operations

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Synthekine

Disqualifiers: CNS manifestations, Gene therapy, Dialysis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 28 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two new treatments, SYNCAR-001 (Autologous CD19 CAR-T Cell Therapy) and STK-009 (Orthogonal IL-2), to determine their effectiveness for severe lupus or scleroderma unresponsive to standard treatments. The researchers aim to find the right dose and assess whether these medicines can safely reduce disease symptoms. Candidates may qualify if they have active, severe lupus or specific types of scleroderma and have not tried certain advanced therapies. For those facing daily challenges from these conditions, this trial might be an option. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that SYNCAR-001 and STK-009 have been safe in early studies. Past trials tested these treatments together for other conditions, and the results showed that patients handled the combination well. Researchers see potential in using it to treat diseases like lupus. Although it's still early, these initial findings are encouraging for those considering joining the trial. As a Phase 1 trial, the main goal is to assess the safety and tolerability of the treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for lupus, which generally include immunosuppressants and corticosteroids, SYNCAR-001 + STK-009 offers a novel approach by using CAR-T cell therapy. This treatment is unique because it involves modifying a patient's own T-cells (autologous cells) to better target and regulate the immune system, potentially offering more precise control of lupus symptoms. Researchers are excited about this treatment because it combines the innovative CAR-T cell therapy with STK-009, administered subcutaneously, which could enhance its effectiveness and reduce side effects compared to traditional treatments. This cutting-edge approach holds promise for providing a more targeted and long-lasting treatment for lupus patients.

What evidence suggests that this trial's treatments could be effective for lupus?

Research shows that the combination of SYNCAR-001 and STK-009, which trial participants will receive, may help treat systemic lupus erythematosus (SLE), a serious disease where the immune system attacks the body. Studies have found that similar treatments using CAR T-cells, a type of immune cell therapy, have successfully improved lupus symptoms. This combination uses a special CAR T-cell and a protein called IL-2 to boost the immune system. Early results suggest positive effects in patients with autoimmune diseases like lupus. Although these findings are preliminary, they offer hope for this treatment method. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with severe, treatment-resistant systemic lupus erythematosus (SLE). Participants must have a clinical diagnosis of SLE and test positive for certain autoantibodies. It's not suitable for those with mild SLE or conditions that could interfere with the study.

Inclusion Criteria

Clinical diagnosis of SLE according to the 2019 European League Rheumatism EULAR/ACR classification criteria

I tested positive for at least one specific antibody related to my condition.

I have severe lupus not affecting my kidneys or active kidney lupus.

Exclusion Criteria

I have or had lupus affecting my brain or spinal cord.

My kidney disease is worsening quickly.

I am on dialysis or my latest kidney biopsy showed chronic damage.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

A single fixed dose of autologous SYNCAR-001 CAR-T is administered intravenously, followed by multiple subcutaneous doses of STK-009

Up to 28 days

Multiple visits for dose escalation and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of adverse events and disease activity

96 weeks

What Are the Treatments Tested in This Trial?

Interventions

• STK-009
• SYNCAR-001

Trial Overview The trial is testing SYNCAR-001 combined with STK-009 as a potential treatment for severe SLE. This phase 1 study aims to evaluate the safety and how well patients tolerate this combination therapy.

How Is the Trial Designed?

Group I: SYNCAR-001 + STK-009 Experimental Treatment 2 Interventions

Dose escalation: A single fixed dose of autologous SYNCAR-001 CAR-T intravenously (IV) will be administered in combination with ascending doses of STK-009 subcutaneously (SC) in non-lymphodepleted patients. Dose expansion: A single fixed dose of autologous SYNCAR-001 CAR-T IV will be administered in combination with STK-009 SC at the RP2D in non-lymphodepleted patients.

STK-009 is already approved in United States for the following indications:

Approved in United States as STK-009 for:

• None approved; under investigation for CD19+ hematologic malignancies and systemic lupus erythematosus (SLE)

Who Is Running the Clinical Trial?

Synthekine

Lead Sponsor

Trials

3

Recruited

290+

Published Research Related to This Trial

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]

Anti-CD19 CAR-T cell therapy demonstrated effective B-cell depletion in a mouse model of systemic lupus erythematosus (SLE), showing both preventive and therapeutic benefits against the disease.

CAR-T cells using the 4-1BB costimulatory motif were found to be more effective than those using the CD28 motif, suggesting a promising strategy for optimizing treatment in SLE.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic efficacy of anti-CD19 CAR-T cells in a mouse model of systemic lupus erythematosus. Jin, X., Xu, Q., Pu, C., et al.[2022]

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]

In a study involving six patients with systemic lupus erythematosus (SLE), researchers successfully produced functional anti-CD19 CAR T cells from their T cells, demonstrating that leukapheresis can yield sufficient T-cell numbers for clinical-scale production despite the challenges posed by autoimmune conditions.

The generated CAR T cells exhibited high expansion rates, viability, and specific cytotoxicity against CD19+ cell lines in vitro, indicating that CAR T-cell therapy can be effectively developed for patients with autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Generation of CD19 Chimeric Antigen Receptor T Cells from Patients with Advanced Systemic Lupus Erythematosus. Kretschmann, S., Völkl, S., Reimann, H., et al.[2023]

In a study involving five patients with severe systemic lupus erythematosus (SLE), treatment with CAR T cells targeting CD19 led to complete remission of the disease in all participants after 3 months, demonstrating high efficacy.

The CAR T cell therapy was well tolerated, with only mild side effects, and patients maintained drug-free remission for an average of 8 months, even after B cells reappeared, indicating a durable response to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 CAR T cell therapy for refractory systemic lupus erythematosus. Mackensen, A., Müller, F., Mougiakakos, D., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06544330

NCT06544330 | A Phase 1 Study of SYNCAR-001 + STK- ... This is a phase 1 study of SYNCAR-001 + STK-009 in patients with severe, refractory systemic autoimmune rheumatic disease.

2. synthekine.com synthekine.com/news/synthekine-presents-positive-initial-results-from-phase-1-clinical-trial-of-cd19-car-t-syncar-001-and-orthogonal-il-2-stk-009-combination-therapy-for-treatment-of-hematologic-malignancies-at-ash-2/

Synthekine Presents Positive Initial Results from Phase 1 ... SYNCAR-001 + STK-009 is a cytokine-enabled cell therapy regimen based on Synthekine's proprietary orthogonal IL-2 technology.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12384554/

Chimeric Antigen Receptor T Cell Immunotherapy for ... Clinical data from case reports and small case series demonstrate profound clinical responses in ARDs, including systemic lupus erythematosus ( ...

4. ddw-online.com ddw-online.com/car-t-and-orthogonal-il-2-therapy-for-lupus-fast-tracked-by-fda-31392-202409/

CAR-T and orthogonal IL-2 therapy for lupus fast-tracked ... “Recent clinical studies have shown CD19 targeted cell therapies can be a potentially effective treatment option for SLE. However, these ...

5. pharmacia.pensoft.net pharmacia.pensoft.net/article/167410/download/pdf/1459281

CAR T-cell therapy in systemic lupus erythematosus was associated with better disease outcomes. The use of an- ti-CD19 CAR T cells has shown promising results in the prevention and treatment ...

6. cgtlive.com cgtlive.com/view/synthekine-cleared-tackle-lupus-car-t-il-2-combination-therapy-us-clinical-trial

Synthekine Cleared to Tackle Lupus With CAR-T and IL-2 ... The data described in this paper demonstrates the potential of STK-009 + SYNCAR-001 to address key limitations of current CD19 CAR-T cell ...