Cevostamab for Multiple Myeloma

(CAMMA 2 Trial)

Not currently recruiting at 53 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called cevostamab (an anti-FcRH5/CD3 T-cell dependent bispecific antibody) to evaluate its effectiveness and safety for people with multiple myeloma, a type of blood cancer that has returned or not responded to other treatments. Participants will receive cevostamab through an IV to assess its effects. The trial targets individuals who have previously tried treatments targeting BCMA (a protein found on myeloma cells) and still experience disease progression. Suitable candidates must have a confirmed diagnosis of multiple myeloma and worsening symptoms despite previous treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new treatment.

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.

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

Research has shown that cevostamab is generally safe for patients with multiple myeloma, a type of blood cancer. Cevostamab, an antibody, helps the immune system find and attack cancer cells, and studies have found it to be well-tolerated by patients. In one study, when combined with other treatments like pomalidomide and dexamethasone, cevostamab was safe and showed early signs of effectiveness against the cancer.

These studies report some side effects, common in cancer treatments. However, the safety data suggest that most patients can handle the treatment without serious issues. The progression of cevostamab to more clinical trials also indicates its safety in humans. For those considering joining a trial, this information offers reassurance about the treatment's tolerability. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Cevostamab is unique because it offers a novel approach for treating multiple myeloma by targeting a protein called FcRH5 on myeloma cells. Unlike traditional treatments like proteasome inhibitors, immunomodulatory drugs, or monoclonal antibodies that focus on different pathways, cevostamab specifically aims at this protein, potentially delivering a more direct attack on the cancer cells. Researchers are excited because this targeted mechanism could provide an effective option for patients who have already undergone other advanced therapies, including BCMA-targeted treatments. This specificity might lead to fewer side effects and improved outcomes for those who have limited treatment options left.

What evidence suggests that cevostamab could be an effective treatment for multiple myeloma?

Research has shown that cevostamab, a type of antibody, may help treat relapsed or refractory multiple myeloma (R/R MM). It aids the body's immune cells, known as T-cells, in attacking cancer cells. Early studies indicate that cevostamab is effective and has manageable side effects for high-risk patients with R/R MM. This trial will evaluate cevostamab in different cohorts, each with specific prior treatments, to determine its effectiveness and safety. The treatment targets a protein called FcRH5 on myeloma cells, enabling the immune system to locate and destroy them. Initial results suggest that cevostamab could offer a new option for patients who haven't had much success with other treatments. ^{3 4 5 6 7}

Who Is on the Research Team?

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Are You a Good Fit for This Trial?

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.

Life expectancy is at least 12 weeks

Agreement to protocol-specified assessments, including bone marrow biopsy and aspirate samples as detailed in the protocol

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. kactusbio.com kactusbio.com/blogs/news/fcrh5-an-emerging-therapeutic-target-in-multiple-myeloma?srsltid=AfmBOoqU80kwG9jtVNfMmaeUdnwcIFg0-WZxL00oNO514cXsdCGG7iSo

FcRh5: An Emerging Therapeutic Target in Multiple Myeloma On Sep 22nd 2025, Roche announced that Cevostamab, a bispecific antibody targeting FcRH5×CD3, is advancing to Phase III clinical trials.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5357723/

Membrane-Proximal Epitope Facilitates Efficient T Cell ... Membrane-proximal epitope facilitates efficient T cell synapse formation by anti-FcRH5/CD3 and is a requirement for myeloma cell killing.

3. onclive.com onclive.com/view/cevostamab-plus-pomalidomide-dexamethasone-is-safe-active-in-r-r-myeloma

Cevostamab Plus Pomalidomide/Dexamethasone Is Safe ... The combination of cevostamab, pomalidomide, and dexamethasone was deemed safe with early efficacy signals in relapsed/refractory multiple ...

4. conference-correspondent.com conference-correspondent.com/highlights/ash/bfcr4350a-a-fcrh5-x-cd3-t-cell-engaging-bispecific-antibody-in-patients-with-rrmm-preliminary-clinical-activity-and-safety

BFCR4350A, a FcRH5 x CD3 T-Cell–Engaging Bispecific ... Preliminary results from the GO39775 study show promising efficacy and manageable toxicity for BFCR4350A as monotherapy in patients with RRMM with high-risk ...

5. en.wikipedia.org en.wikipedia.org/wiki/Cevostamab

Cevostamab Cevostamab is a bispecific T-cell engager antibody that facilitates T cell-mediated killing of multiple myeloma cells through a dual-targeting mechanism.

6. withpower.com withpower.com/trial/phase-1-multiple-myeloma-8-2017-ee41e

Cevostamab for Multiple Myeloma · Info for Participants The safety data for Cevostamab, also known as anti-FcRH5/CD3 T ... The bispecific antibody BiFab-BCMA effectively redirects T cells to attack multiple myeloma ...

7. kactusbio.com kactusbio.com/blogs/news/fcrh5-an-emerging-therapeutic-target-in-multiple-myeloma?srsltid=AfmBOoqO3RAWmZCQqshbtVStrrPFozckLSge4_nPkOTiXkvwZNHGv4G_

FcRh5: An Emerging Therapeutic Target in Multiple Myeloma On Sep 22nd 2025, Roche announced that Cevostamab, a bispecific antibody targeting FcRH5×CD3, is advancing to Phase III clinical trials.