CB-011 for Multiple Myeloma

(CaMMouflage Trial)

Recruiting at 20 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

Trial Summary

What is the purpose of this trial?

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 cell maturation antigen (BCMA), to determine the best dose of CB-011, and to assess the effectiveness of CB-011 in treating multiple myeloma that has come back (relapsed) or that is no longer responding to other treatment (refractory).

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.

What data supports the effectiveness of the treatment CB-011 for Multiple Myeloma?

Research shows that similar treatments using CAR T cells targeting BCMA have been effective in reducing tumor burden and prolonging survival in preclinical models of multiple myeloma. Additionally, early clinical trials have shown that these therapies can induce complete and lasting responses in patients with relapsed or hard-to-treat multiple myeloma. ^{1 2 3 4 5}

What is known about the safety of CB-011 (CRISPR-Edited Allogeneic Anti-BCMA CAR-T Cell Therapy) for multiple myeloma?

CB-011, a type of CAR T-cell therapy targeting BCMA, has shown a manageable safety profile in clinical trials for multiple myeloma. Common side effects include cytokine release syndrome (a condition where the immune system releases too many proteins into the blood too quickly), which was mostly mild to moderate and reversible. No severe neurotoxicity (damage to the nervous system) was observed, and no dose-limiting toxicities were reported. ^{1 6 7 8 9}

How is the CB-011 treatment different from other treatments for multiple myeloma?

CB-011 is unique because it uses CRISPR-edited T cells from healthy donors, making it an 'off-the-shelf' treatment that can be used immediately, unlike traditional CAR T-cell therapies that require a lengthy process to modify a patient's own cells. This approach also includes a safety feature that allows the cells to be eliminated if needed, potentially reducing side effects. ^{1 4 10 11 12}

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Preclinical Evaluation of Allogeneic CAR T Cells Targeting BCMA for the Treatment of Multiple Myeloma. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

CRISPR-based screens uncover determinants of immunotherapy response in multiple myeloma. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Vγ9Vδ2 T cells expressing a BCMA-Specific chimeric antigen receptor inhibit multiple myeloma xenograft growth. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Sending CAR T Cells After Multiple Myeloma. [2018]

5. United States 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. [2023]

6. United States 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. [2019]

7. Italy 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. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

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

9. England 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. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy in Multiple Myeloma: Mission Accomplished? [2023]

12. United States 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. [2022]