Cevostamab for Multiple Myeloma

(CAMMA 2 Trial)

Recruiting at 49 trial locations

Overseen By Reference Study ID Number: CO43476 https://forpatients.roche.com

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hoffmann-La Roche

Must not be taking: Immunosuppressants, Antivirals, Chemotherapy, others

Disqualifiers: Pregnancy, Autoimmune disease, CNS disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

90 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a medication called cevostamab for patients whose multiple myeloma has returned or not responded to other treatments. It works by helping the immune system target and destroy cancer cells.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that you should not have had certain treatments like chemotherapy, radiotherapy, or other anti-cancer agents within 4 weeks before starting the study. It's best to discuss your specific medications with the study team.

What data supports the effectiveness of the drug Cevostamab for treating multiple myeloma?

Research shows that the anti-FcRH5/CD3 bispecific antibody, which is part of Cevostamab, can effectively kill myeloma cells and deplete B cells in animal models. This suggests potential effectiveness in treating multiple myeloma, similar to other bispecific antibodies that have shown high response rates in early clinical trials. ^{1 2 3 4 5}

Is Cevostamab safe for humans?

Cevostamab, also known as anti-FcRH5/CD3, has been studied for its safety in humans. In clinical trials, similar treatments have shown side effects like cytokine release syndrome (a condition where the immune system releases too many proteins into the blood too quickly) and neurotoxicity (damage to the nervous system), with varying incidence rates. These side effects are important to consider when evaluating the safety of Cevostamab. ^{3 4 6 7 8}

How is the drug Cevostamab different from other treatments for multiple myeloma?

Cevostamab is unique because it is a bispecific antibody that targets the FcRH5 protein on multiple myeloma cells and CD3 on T cells, facilitating the immune system's ability to attack cancer cells. This mechanism is different from other treatments that may target different proteins or use different methods to engage the immune system. ^{1 3 4 6 9}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for adults with relapsed/refractory multiple myeloma who have previously been treated with BCMA-targeted therapies and are triple-class refractory. They should expect to live at least 12 weeks, be able to perform daily activities (ECOG status of 0 or 1), and agree to use contraception if necessary. People can't join if they've had certain medical conditions, recent drug abuse, severe allergies to monoclonal antibodies, or are pregnant.

Inclusion Criteria

My side effects from previous cancer treatments are mild or gone.

I am fully active or can carry out light work.

Life expectancy is at least 12 weeks

Exclusion Criteria

I do not have an active infection or have not been treated with IV antibiotics in the last 14 days.

I have hepatitis C.

History of severe allergic or anaphylactic reactions to mAb therapy

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cevostamab via intravenous (IV) infusion in different cohorts with specific dosing regimens

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

Treatment Details

Interventions

• Cevostamab

Trial Overview The study tests the effectiveness and safety of a drug called Cevostamab given through IV infusion in patients whose multiple myeloma has not responded to previous treatments. It also looks at how the body processes the drug. Tocilizumab may be used as part of treatment management.

Participant Groups

Group I: Cohort B2: Prior BCMA Bispecific Experimental Treatment 2 Interventions

Expansion Cohort B2 will be opened, after the initial results from Cohort A2, at the same dose as per Cohort B1.

Group II: Cohort B1: Prior BCMA CAR-T Experimental Treatment 2 Interventions

Participants enrolled in expansion Cohort B1, will be given cevostamab at the selected dosing regimen.

Group III: Cohort A2: Prior BCMA Bispecific Experimental Treatment 2 Interventions

Participants enrolled into exploratory Cohort A2 will receive the same dosing regimen as Cohort A1.

Group IV: Cohort A1: Prior BCMA antibody-drug conjugate (ADC) or chimeric antigen receptor T (CAR-T) Experimental Treatment 2 Interventions

Participants in Cohort A1 will be treated at the double step-up split dosing regimen.

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Findings from Research

The bispecific antibody BiFab-BCMA effectively redirects T cells to attack multiple myeloma cells, showing up to 20 times greater potency than a similar antibody targeting CS1.

BiFab-BCMA not only activates T cells in laboratory settings but also leads to rapid tumor regression in animal models, suggesting it could be a promising alternative to existing CAR-T therapies for treating multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An anti-B cell maturation antigen bispecific antibody for multiple myeloma. Ramadoss, NS., Schulman, AD., Choi, SH., et al.[2015]

Bispecific antibodies targeting antigens like BCMA, GPRC5D, and FcRH5 show a favorable safety profile in early-phase clinical trials for multiple myeloma, with low-grade side effects such as cytokine release syndrome and infections.

Preliminary efficacy data indicate response rates between 61% and 83% in heavily treated patients, suggesting that bispecific antibodies could become a key treatment option for multiple myeloma, although further studies are needed to confirm long-term effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific Antibodies in Multiple Myeloma: Present and Future. Lancman, G., Sastow, DL., Cho, HJ., et al.[2023]

The anti-FcRH5/CD3 bispecific antibody effectively activates T cells and induces the death of multiple myeloma cells at very low concentrations, showcasing its potential as a powerful treatment for this cancer.

In preclinical studies with cynomolgus monkeys, the antibody led to complete depletion of B cells and plasma cells in the bone marrow, indicating strong efficacy and potential for use in combination therapies targeting PD-1/PD-L1 signaling.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Membrane-Proximal Epitope Facilitates Efficient T Cell Synapse Formation by Anti-FcRH5/CD3 and Is a Requirement for Myeloma Cell Killing. Li, J., Stagg, NJ., Johnston, J., et al.[2022]

Three new bispecific antibodies—teclistamab, elranatamab, and talquetamab—have received accelerated FDA approval for treating relapsed/refractory multiple myeloma, indicating their potential efficacy in this challenging condition.

While these agents show promise, the medical community is currently awaiting results from randomized phase III clinical trials to better understand their effectiveness compared to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Embarrassment of Riches: Three FDA-Approved Bispecific Antibodies for Relapsed Refractory Multiple Myeloma. Firestone, R., Lesokhin, AM., Usmani, SZ.[2023]

Teclistamab, a bispecific antibody targeting BCMA and CD3, showed a high overall response rate of 64% in a real-world study of 52 patients with relapsed/refractory multiple myeloma, including a 50% response rate in those previously treated with anti-BCMA therapies.

Immune profiling revealed that higher levels of effector CD8+ T-cells were linked to better responses to teclistamab, while regulatory T-cells were associated with nonresponse, suggesting that immune status could serve as a useful biomarker for treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD8 effector T cells enhance response in BCMA-exposed and -naïve multiple myeloma. Firestone, RS., McAvoy, D., Shekarkhand, T., et al.[2023]

Teclistamab, a newly FDA-approved bispecific antibody, effectively targets both T-cells and myeloma cells, showing durable responses in patients with relapsed/refractory multiple myeloma who have failed multiple prior therapies, as demonstrated in the MajesTEC-1 study.

As the first bispecific antibody approved for multiple myeloma, teclistamab offers a new treatment option for patients with limited choices, and ongoing trials are exploring its use alongside other novel bispecific antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Newly approved and forthcoming T-cell-redirecting bispecific antibodies for the treatment of relapsed/refractory multiple myeloma. Granger, K., Gaffney, KJ., Davis, JA.[2023]

Emerging bispecific antibody therapies targeting proteins like BCMA and GPRC5D show promising efficacy in treating relapsed/refractory multiple myeloma, with response rates between 50-80% in heavily pretreated patients.

While these therapies offer a more readily available option compared to CAR-T cell therapy, they also carry risks of adverse events such as cytokine release syndrome (40-90% incidence) and neurotoxicity (3-20% incidence), highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T cell redirecting bispecific antibodies for multiple myeloma: emerging therapeutic strategies in a changing treatment landscape. Kazandjian, D., Kowalski, A., Landgren, O.[2023]

ELREXFIO™ (elranatamab-bcmm) is an FDA-approved bispecific antibody that effectively targets both CD3 and BCMA, activating T-cells to attack multiple myeloma cells, which is crucial for patients with relapsed or refractory cases.

Clinical trials, including MagnetisMM-3, have shown significant response rates and long-term tolerability for ELREXFIO, indicating its potential to improve treatment outcomes for patients suffering from this challenging cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elrexfio™ (elranatamab-bcmm): The game-changer in treatment of multiple myeloma. Rais, T., Khan, A., Riaz, R.[2023]

The novel bispecific antibody bscWue-1 x CD3 effectively induces T-cell-mediated cell death in multiple myeloma cells, demonstrating efficacy in 9 out of 11 patient cases tested.

This antibody shows promise for targeted therapy as it selectively kills Wue-1 antigen-positive myeloma cells, even at low effector-to-target cell ratios, suggesting a potential for effective treatment with minimal side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel recombinant bispecific single-chain antibody, bscWue-1 x CD3, induces T-cell-mediated cytotoxicity towards human multiple myeloma cells. Hönemann, D., Kufer, P., Rimpler, MM., et al.[2017]

References

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

An anti-B cell maturation antigen bispecific antibody for multiple myeloma. [2015]

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

Bispecific Antibodies in Multiple Myeloma: Present and Future. [2023]

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

Membrane-Proximal Epitope Facilitates Efficient T Cell Synapse Formation by Anti-FcRH5/CD3 and Is a Requirement for Myeloma Cell Killing. [2022]

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

An Embarrassment of Riches: Three FDA-Approved Bispecific Antibodies for Relapsed Refractory Multiple Myeloma. [2023]

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

CD8 effector T cells enhance response in BCMA-exposed and -naïve multiple myeloma. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Newly approved and forthcoming T-cell-redirecting bispecific antibodies for the treatment of relapsed/refractory multiple myeloma. [2023]

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

T cell redirecting bispecific antibodies for multiple myeloma: emerging therapeutic strategies in a changing treatment landscape. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Elrexfio™ (elranatamab-bcmm): The game-changer in treatment of multiple myeloma. [2023]

9. England pubmed.ncbi.nlm.nih.gov

A novel recombinant bispecific single-chain antibody, bscWue-1 x CD3, induces T-cell-mediated cytotoxicity towards human multiple myeloma cells. [2017]