CB-011 for Multiple Myeloma

(CaMMouflage Trial)

Recruiting at 21 trial locations

Overseen By Caribou Biosciences

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Caribou Biosciences, Inc.

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days for Part A, followed by Part B

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to test the safety and determine the optimal dose of a new treatment called CB-011, which uses specially modified cells (CAR-T cell therapy) to target and fight multiple myeloma, a type of blood cancer. The focus is on helping patients whose cancer has relapsed or become refractory to other treatments. It suits those with multiple myeloma who have already tried at least three different standard treatments, including a proteasome inhibitor and an anti-CD38 antibody, and are still facing challenges. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity 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 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 CB-011 is likely to be safe for humans?

Research has shown that CB-011, a type of cell therapy, is being tested to treat multiple myeloma, a kind of blood cancer. In a recent study, patients who received CB-011 tolerated it well, and many showed a positive response to the treatment.

Although specific safety details from the study aren't provided here, this is a Phase 1 study, meaning researchers are closely monitoring for any serious side effects. At this stage, the main goal is to determine the best dose while checking for any negative reactions. So far, the results appear promising, and the treatment is advancing in research.

Anyone considering joining a clinical trial should discuss the possible risks and benefits with their doctor. This ensures they have the most current and personalized information. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for multiple myeloma, like chemotherapy, immunomodulatory drugs, and proteasome inhibitors, CB-011 offers a novel approach by using gene-edited T-cells to target cancer cells. Researchers are excited because CB-011 is designed to enhance the immune system's ability to recognize and kill myeloma cells more effectively. By modifying T-cells to better target the disease, CB-011 has the potential to improve outcomes for patients with multiple myeloma where existing therapies may not be sufficient.

What evidence suggests that CB-011 might be an effective treatment for multiple myeloma?

Research has shown that CB-011, the investigational treatment in this trial, is a promising therapy for multiple myeloma, a cancer affecting the bone marrow. CB-011 is a type of CAR-T cell therapy, which uses specially modified immune cells to find and destroy cancer cells. This treatment targets a protein called BCMA, found on multiple myeloma cells. Early studies suggest that this therapy can enhance the body's ability to fight cancer by strengthening the response against tumors. Although more research is needed, initial results offer hope for patients whose multiple myeloma has returned or not responded to other treatments. ^{2 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for adults with multiple myeloma that has returned or isn't responding to treatment. They must have tried at least three types of treatments, including specific inhibitors and antibodies. Good performance status and organ function are required. People who've had certain stem cell transplants recently, previous CAR-T therapy, CNS involvement, recent stroke or seizure, HIV, live vaccines within 4 weeks before the study starts, or hepatitis B/C can't join.

Inclusion Criteria

I am fully active or can carry out light work.

My blood, kidney, liver, lung, and heart functions are all within normal ranges.

I've had 3 or more treatments for my multiple myeloma, including a PI, an IMiD, and an anti-CD38.

Exclusion Criteria

I am HIV positive or have a history of HIV.

My cancer has spread to or affected my brain or spinal cord.

Known life-threatening allergies, hypersensitivity, or intolerance to CB-011 or its excipients.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CB-011 in ascending doses using a traditional 3+3 design in Part A, followed by Part B where up to 30 participants receive CB-011 at the recommended dose

28 days for Part A, followed by Part B

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• CB-011

Trial Overview The trial is testing CB-011: a new type of 'off-the-shelf' CAR-T cell therapy targeting BCMA in patients whose multiple myeloma has relapsed or is refractory. It's a Phase 1 study focusing on safety and finding the right dose while also checking how well it works against this cancer.

How Is the Trial Designed?

Group I: CB-011 Experimental Treatment 1 Intervention

* Part A Escalation with CB-011 in ascending doses using a traditional 3+3 design. * Part B Expansion. Up to 30 participants will be enrolled to receive CB-011 at the RDE/MTD and/or RP2D determined in Plan A

CB-011 is already approved in United States for the following indications:

Approved in United States as CB-011 for:

• None approved; under investigation for Relapsed/Refractory Multiple Myeloma

Who Is Running the Clinical Trial?

Caribou Biosciences, Inc.

Lead Sponsor

Trials

5

Recruited

360+

Published Research Related to This Trial

In a study involving 35 patients with relapsed or refractory multiple myeloma, the CAR T-cell therapy ARI0002h achieved a remarkable overall response rate of 100% within the first 100 days, with 80% of patients showing a very good partial response or better.

The treatment demonstrated a favorable safety profile, with 80% of patients experiencing only mild cytokine-release syndrome (grade 1-2) and no neurotoxic events reported, suggesting that ARI0002h could be a safe and effective option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fractionated initial infusion and booster dose of ARI0002h, a humanised, BCMA-directed CAR T-cell therapy, for patients with relapsed or refractory multiple myeloma (CARTBCMA-HCB-01): a single-arm, multicentre, academic pilot study. Oliver-Caldés, A., González-Calle, V., Cabañas, V., et al.[2023]

Using CRISPR technology, researchers identified that inhibiting HDAC7 and the Sec61 complex can increase the expression of the BCMA antigen on multiple myeloma cells, which may help overcome resistance to immunotherapy.

The study found that combining Sec61 inhibition with a BCMA-targeted antibody-drug conjugate improved its effectiveness against myeloma, suggesting new strategies for enhancing cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CRISPR-based screens uncover determinants of immunotherapy response in multiple myeloma. Ramkumar, P., Abarientos, AB., Tian, R., et al.[2021]

Anti-BCMA CAR T cells derived from healthy donors showed better T-cell fitness and cytotoxic activity against multiple myeloma cells compared to those derived from patients, indicating a potential advantage in using allogeneic T cells for treatment.

The study demonstrated that these healthy donor-derived CAR T cells could effectively kill primary multiple myeloma cells in the bone marrow microenvironment, suggesting they could be a promising therapeutic strategy for relapsed multiple myeloma patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic Anti-BCMA CAR T Cells Are Superior to Multiple Myeloma-derived CAR T Cells in Preclinical Studies and May Be Combined with Gamma Secretase Inhibitors. Metelo, AM., Jozwik, A., Luong, LA., et al.[2023]

In a first-in-humans clinical trial involving 16 patients with heavily treated multiple myeloma, CAR-BCMA T cells demonstrated an impressive overall response rate of 81%, with 63% achieving very good partial or complete responses.

The treatment was associated with significant anti-myeloma activity, including eradication of bone marrow myeloma and resolution of soft-tissue plasmacytomas, although some patients experienced severe but reversible cytokine-release syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T Cells Genetically Modified to Express an Anti-B-Cell Maturation Antigen Chimeric Antigen Receptor Cause Remissions of Poor-Prognosis Relapsed Multiple Myeloma. Brudno, JN., Maric, I., Hartman, SD., et al.[2019]

B-cell maturation antigen (BCMA) CAR T cells are emerging as a highly effective treatment for multiple myeloma, showing promise for inclusion in first-line therapy based on clinical and preclinical data.

Advancements in patient stratification through genomic analysis and improvements in CAR T-cell manufacturing are enhancing early diagnosis, management of side effects, and overall access to this innovative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy in Multiple Myeloma: Mission Accomplished? Rasche, L., Hudecek, M., Einsele, H.[2023]

Allogeneic CAR T therapies, which use T cells from healthy donors, may address the limitations of autologous CAR T therapies, such as long manufacturing times and potential complications.

The study demonstrated that allogeneic BCMA CAR T cells, engineered with gene-editing technology and an off switch for safety, showed sustained antitumor responses in mice, making them a promising candidate for future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Evaluation of Allogeneic CAR T Cells Targeting BCMA for the Treatment of Multiple Myeloma. Sommer, C., Boldajipour, B., Kuo, TC., et al.[2020]

In a phase 1 study of 33 patients with relapsed or refractory multiple myeloma, the CAR T-cell therapy bb2121 demonstrated a high objective response rate of 85%, with 45% of patients achieving complete responses.

While bb2121 showed promising antitumor activity, it also had significant safety concerns, with 76% of patients experiencing cytokine release syndrome and 42% experiencing neurological toxic effects, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma. Raje, N., Berdeja, J., Lin, Y., et al.[2021]

In a phase II trial involving 69 patients with relapsed or refractory multiple myeloma, the combination of anti-BCMA and anti-CD19 CAR T cells resulted in a high overall response rate of 92%, with 60% achieving a complete response.

The treatment demonstrated a median progression-free survival of 18.3 months and a manageable safety profile, although 95% of patients experienced cytokine release syndrome, indicating the need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Follow-Up of Combination of B-Cell Maturation Antigen and CD19 Chimeric Antigen Receptor T Cells in Multiple Myeloma. Wang, Y., Cao, J., Gu, W., et al.[2022]

Chimeric antigen receptor T cells targeting the BCMA protein show promise as a potent treatment for multiple myeloma, based on preliminary results from an ongoing phase I clinical trial in China.

The therapy was well tolerated by patients and led to complete and durable responses in those with relapsed or refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sending CAR T Cells After Multiple Myeloma. [2018]

HBI0101, a novel anti-BCMA CAR T-cell therapy, demonstrated a high overall response rate of 75% in a phase I study involving 20 heavily pre-treated patients with relapsed/refractory multiple myeloma, with a dose-dependent increase in efficacy observed in higher doses.

The therapy showed a manageable safety profile, with 90% of patients experiencing only mild cytokine release syndrome and no severe toxicities, indicating that HBI0101 could be a safe and effective treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and manufacture of novel locally produced anti-BCMA CAR T cells for the treatment of relapsed/refractory multiple myeloma: results from a phase I clinical trial. Asherie, N., Kfir-Erenfeld, S., Avni, B., et al.[2023]

BCMA CAR T-cell therapy has shown impressive response rates of 60% to 100% in patients with relapsed/refractory myeloma, indicating its potential as a highly effective treatment option.

While the therapy can lead to severe but reversible toxicities like cytokine release syndrome and neurotoxicity, ongoing studies aim to enhance its safety and efficacy through combinations with other treatments and gene editing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cells and Other Cellular Therapies for Multiple Myeloma: 2018 Update. Cohen, AD.[2019]

Modified Vγ9Vδ2 T cells, engineered with a BCMA-specific CAR, showed strong ability to kill multiple myeloma cells while leaving normal cells unharmed, indicating a targeted and effective approach to treatment.

In a mouse model, treatment with these CAR-modified T cells, combined with Zometa, significantly reduced tumor burden and improved survival rates, suggesting promising potential for this therapy in human patients with multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vγ9Vδ2 T cells expressing a BCMA-Specific chimeric antigen receptor inhibit multiple myeloma xenograft growth. Zhang, X., Ng, YY., Du, Z., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05722418

NCT05722418 | CRISPR-Edited Allogeneic Anti-BCMA ... This is a Phase 1 study to evaluate the safety of CB-011 (the study treatment), an allogeneic chimeric antigen receptor (CAR-T) cell therapy that targets the B ...

2. investor.cariboubio.com investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-announces-fda-clearance-ind-application-cb

Release details CB-011 is the first allogeneic anti-BCMA CAR-T cell therapy, to Caribou's knowledge, that is engineered to improve persistence of antitumor response.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10985478/

High-Specificity CRISPR-Mediated Genome Engineering ... CB-011 is a hypoimmunogenic, allogeneic anti–B-cell maturation antigen (BCMA) CAR T cell therapy candidate. CB-011 cells feature 4 genomic alterations and were ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2023-01891

CRISPR-Edited Allogeneic Anti-BCMA CAR-T Cell ... This is a Phase 1 study to evaluate the safety of CB-011 (the study treatment), an allogeneic chimeric antigen receptor (CAR-T) cell therapy that targets the B ...

5. duke-research.dukehealth.org duke-research.dukehealth.org/studies/pro00112753

CB-011 CRISPR Allogeneic Anti-BCMA CART in patients with ... We are doing this study to find out if an experimental therapy called CB-011 (the study drug) is a safe and effective option for people who have relapsed or ...

6. investor.cariboubio.com investor.cariboubio.com/news-releases/news-release-details/caribou-biosciences-announces-positive-data-cammouflage-phase-1

Release details CB-011 is an allogeneic anti-BCMA CAR-T cell therapy being evaluated in patients with relapsed or refractory multiple myeloma (r/r MM) in the ...

7. finance.yahoo.com finance.yahoo.com/news/caribou-biosciences-announces-positive-data-120000438.html

Caribou Biosciences Announces Positive Data from ... First clinical data disclosure for CB-011 highlights its potential as a best-in-class allogeneic CAR-T cell therapy for relapsed or ...

8. investor.cariboubio.com investor.cariboubio.com/static-files/b48ff056-ff4f-478a-88f2-4f53f9746d03

Vispa-cel for r/r LBCL • CB-011 for r CB-011: allogeneic anti-BCMA CAR-T cell therapy armored with immune cloaking to reduce T and NK cell rejection. CB-011. B2M–HLA-E. Anti-BCMA.

9. stocktitan.net stocktitan.net/news/CRBU/caribou-biosciences-announces-positive-data-from-ca-m-mouflage-phase-la0ji00s4wh2.html

Caribou Biosciences' CB-011 Shows 92% ORR in Phase 1 ... CB-011 shows 92% ORR, 75% ≥CR in 12-patient BCMA-naïve cohort at RDE; 91% MRD negative, follow-up 8.3 months. 450M-cell RDE; expansion 2025, ...