CB-010 for Lupus

(GALLOP Trial)

Overseen By Caribou Biosciences

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Caribou Biosciences, Inc.

Must be taking: Glucocorticoids, Immunosuppressives

Must not be taking: Live vaccines

Disqualifiers: CNS lupus, HIV, Hepatitis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CRISPR-Edited Allogeneic Anti-CD19 CAR-T Cell Therapy (CB-010) to determine its safety and effectiveness for people with difficult-to-treat Systemic Lupus Erythematosus (SLE). Participants are divided into two groups: one for those with lupus affecting the kidneys (lupus nephritis) and another for those with lupus affecting other body parts. Ideal candidates have had SLE for at least six months and have not responded well to standard treatments like steroids and other immune suppressants. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that participants should be refractory (not responding) to certain treatments, which might imply that you should continue your current medications if they are not effective.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that CB-010, a new treatment using CRISPR technology, appears safe for treating systemic lupus. In studies with lymphoma patients, CB-010 was generally well tolerated and significantly reduced B cells, a type of immune cell. This suggests it might be similarly safe for people with lupus.

The treatment is currently in its first phase of testing, focusing primarily on safety. Researchers are closely monitoring for any side effects to ensure safety. Early results have not revealed any serious safety issues.

Additionally, the FDA has approved further testing of the therapy, indicating a positive safety profile. This approval typically means the treatment has passed initial safety checks, although more data will be gathered as trials continue.

Overall, while the results are promising, it is important to remember that this is an early-stage trial. Researchers will closely monitor participants to ensure their well-being. ^{1 2 3 4 5}

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

Researchers are excited about CB-010 because it brings a novel approach to treating lupus. Unlike standard treatments like immunosuppressants and corticosteroids, which broadly dampen the immune system, CB-010 is a CRISPR-edited, allogeneic CAR-T cell therapy specifically targeting CD19, a protein found on certain immune cells. This targeted action could potentially offer more precise control over the immune response, reducing lupus symptoms while minimizing side effects. Additionally, because it is allogeneic, CB-010 offers the advantage of being an off-the-shelf therapy, which could make it more accessible and convenient for patients.

What evidence suggests that this treatment might be an effective treatment for lupus?

Research has shown that CRISPR-edited allogeneic anti-CD19 CAR-T cell therapy, such as CB-010, holds promise for treating systemic lupus erythematosus (SLE). Laboratory studies have found that similar therapies can target and remove certain B cells, immune cells involved in SLE. Removing these cells can lead to lasting symptom improvements. The trial will evaluate CB-010 in two separate cohorts: one for lupus nephritis (LN) and another for extrarenal lupus (ERL). This therapy specifically targets a protein called CD19 on these B cells, enhancing precision. Early results suggest that this approach could help manage LN and ERL by reducing inflammation and preventing organ damage. ^{1 2 4 5 6}

Are You a Good Fit for This Trial?

This trial is for patients with severe lupus, specifically those with Class III or IV lupus nephritis and a high protein-to-creatinine ratio in their urine. Participants must have tried at least two immunosuppressive therapies without success and be up to date on vaccinations. Women of childbearing age must use effective contraception.

Inclusion Criteria

My condition did not improve after using steroids and two other immune-suppressing drugs.

I have been diagnosed with lupus for at least 6 months.

I have severe lupus affecting my kidneys.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single infusion of CB-010

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• CRISPR-Edited Allogeneic Anti-CD19 CAR-T Cell Therapy

Trial Overview The GALLOP study is testing the safety and effectiveness of CB-010, a CRISPR-edited anti-CD19 CAR-T cell therapy. This Phase 1 trial involves one infusion for people with refractory Systemic Lupus Erythematosus (SLE), including both kidney-involved (lupus nephritis) and non-kidney (extrarenal) cases.

How Is the Trial Designed?

Group I: Cohort 2 Extrarenal Lupus (ERL) Experimental Treatment 1 Intervention

Group II: Cohort 1 Lupus Nephritis (LN) Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Caribou Biosciences, Inc.

Lead Sponsor

Trials

5

Recruited

360+

Published Research Related to This Trial

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]

Complete and sustained depletion of CD19+ B cells using CD19-targeted CAR T cells was shown to be a highly effective therapy in lupus models, significantly reversing disease symptoms and extending lifespan in mouse models of lupus.

This approach demonstrated long-lasting effects, with CAR T cells remaining active for up to one year, suggesting that sustained B cell depletion could be a promising strategy for treating lupus in humans, warranting further clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sustained B cell depletion by CD19-targeted CAR T cells is a highly effective treatment for murine lupus. Kansal, R., Richardson, N., Neeli, I., et al.[2021]

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]

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 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/NCT06752876

CRISPR-Edited Allogeneic Anti-CD19 CAR-T Cell Therapy ... This is a Phase 1 study to evaluate the safety and efficacy of a single infusion of CB-010 in patients with refractory Systemic Lupus Erythematosus (SLE) with ...

2. jrheum.org jrheum.org/content/52/Suppl_1/147.3

A PHASE 1, MULTICENTER, OPEN-LABEL STUDY OF CB ... GALLOP is a Phase 1 clinical trial evaluating CB-010 in the treatment of LN and ERL, which has the potential to overcome key barriers to access to CAR-T cell ...

3. investor.cariboubio.com investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-initiates-cb-010-gallop-phase-1-trial-lupus

Caribou Biosciences Initiates the CB-010 GALLOP Phase ... Caribou Biosciences Initiates the CB-010 GALLOP Phase 1 Trial in Lupus and Provides Outlook for Multiple Clinical Datasets in 2025 · Clinical ...

4. acrabstracts.org acrabstracts.org/abstract/preclinical-analysisof-cb-010-an-allogeneic-anti-cd19car-t-cell-therapywith-a-pd-1-knockout-for-the-treatment-of-patients-with-refractory-systemic-lupus-erythematosus-sle/

Preclinical Analysisof CB-010, an Allogeneic anti- ... Background/Purpose: Autologous CD19-directed CAR-T cell therapy has been shown to eradicate aberrant B cells leading to durable clinical responses in SLE ...

5. bloodcancerunited.org bloodcancerunited.org/research/therapy-acceleration-program-tap/portfolio/caribou-biosciences

Caribou Biosciences April 4, 2024 - announced FDA clearance for CB-010, an allogeneic anti-CD19 CAR-T cell therapy with a PD-1 knockout (KO), for the treatment of lupus nephritis ( ...

6. cariboubio.com cariboubio.com/file.cfm/11/docs/cb-010_lupus_preclinica_poster_acr2024_final.pdf

Preclinical Analysis of CB-010, an Allogeneic anti-CD19 ... In the ANTLER Phase 1 trial in lymphoma patients, CB-010 led to deep B cell depletion, extended B cell aplasia, and was generally well tolerated ...