Cevostamab Following CAR T Cell Therapy for Multiple Myeloma

Overseen By Sara Whittington

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Pennsylvania

Must be taking: Proteasome inhibitors, IMiDs, Anti-CD38

Must not be taking: Immunotherapeutics, Immunosuppressants

Disqualifiers: Pregnancy, Autoimmune disease, CNS disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 8

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This clinical trial aims to evaluate the effectiveness of cevostamab, a T-cell dependent bispecific antibody, for individuals with multiple myeloma, a type of blood cancer, following CAR T cell therapy. The study will determine if adding cevostamab can help patients achieve a deep remission (no detectable cancer) at 12 months. Participants must have previously undergone a specific CAR T cell therapy and not shown disease progression afterward. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take certain immunosuppressive medications or other anti-cancer agents close to the start of the trial, and there is a 2-week washout period for some treatments. It's best to discuss your specific medications with the trial team.

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

Research shows that cevostamab, a type of antibody treatment, is generally well-tolerated by patients with relapsed or hard-to-treat multiple myeloma. Earlier studies demonstrated promising results with manageable side effects. Some patients experienced side effects, but these were usually not severe. The treatment helps the body's immune cells, called T cells, find and destroy cancer cells. Importantly, cevostamab is now undergoing testing in more advanced clinical trials, indicating researchers' confidence in its safety so far. While side effects exist, they are considered acceptable compared to the potential benefits of the treatment. ^{1 2 3 4 5}

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

Unlike the standard of care for multiple myeloma, which often includes drugs like proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies targeting CD38, cevostamab offers a fresh approach by engaging a different mechanism. Cevostamab is a bispecific antibody that specifically targets both the Fc receptor-like 5 (FCRL5) on myeloma cells and CD3 on T cells, effectively directing the body's own immune system to recognize and attack cancer cells. Researchers are excited about cevostamab because it could potentially overcome resistance issues seen in other treatments and bring renewed hope for patients who have relapsed after CAR T cell therapy.

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

Research shows that cevostamab holds promise for treating relapsed or refractory multiple myeloma, a type of blood cancer. In this trial, participants will receive cevostamab, which studies have found activates T cells—immune cells that can target and kill cancer cells. Early results from previous patients indicate that cevostamab works effectively and has manageable side effects when used alone. It targets specific proteins on cancer cells, enabling the immune system to attack and destroy them. This approach offers hope for patients who haven't responded to other treatments. ^{2 3 6 7 8}

Who Is on the Research Team?

Adam D Cohen, MD

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for adults over 18 with relapsed/refractory multiple myeloma who've had at least four prior treatments, including a proteasome inhibitor, IMiD, and anti-CD38 antibody. They must have undergone BCMA-directed CAR T cell therapy recently without disease progression and be able to follow the study plan.

Inclusion Criteria

Agreement for contraception for women of childbearing potential

I can join the study even if my disease can't be measured.

Signed Informed Consent Form(s)

Exclusion Criteria

I have had cancer before that might affect this study's results.

History of specific autoimmune diseases

I have not had major surgery recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4-6 weeks

Safety Run-in

Initial safety run-in period to assess safety and tolerability of cevostamab

4 weeks

Treatment

Cevostamab is administered as an IV infusion once every 3 weeks for 8 cycles

24 weeks

8 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

What Are the Treatments Tested in This Trial?

Interventions

• Cevostamab

Trial Overview

The study tests Cevostamab given intravenously every three weeks starting about ten weeks after CAR T cell therapy. The goal is to see if it improves complete remission rates at 12 months post-CAR T treatment in patients with multiple myeloma.

How Is the Trial Designed?

Group I: Cevostamab Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD

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]

Patients with multiple myeloma who do not respond to existing therapies have limited survival, but new treatments like CAR T-lymphocytes, bispecific antibodies, and antibody-drug conjugates are showing promise in early trials.

Idecabtagene vicleucel (ide cel) and belantamab mafodotin (belamaf) have been approved for use in relapsed/refractory multiple myeloma based on positive results from phase 2 studies, indicating their potential effectiveness in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cells, bispecific antibodies, and antibody-drug conjugates for multiple myeloma: An update. Lakshman, A., Kumar, SK.[2022]

In a phase I clinical trial involving 30 multiple myeloma patients, anti-BCMA CAR T cells showed favorable safety with no high-grade cytokine release syndrome and only one case of low-grade neurologic toxicity.

The treatment demonstrated significant efficacy, with 10 out of 15 patients with measurable disease achieving a partial response or better, and 4 patients converting to minimal residual disease-negative complete response, indicating strong antimyeloma activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-BCMA/CD19 CAR T Cells with Early Immunomodulatory Maintenance for Multiple Myeloma Responding to Initial or Later-Line Therapy. Garfall, AL., Cohen, AD., Susanibar-Adaniya, SP., et al.[2023]

The introduction of second-generation proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies has significantly improved survival rates for multiple myeloma patients, but many still relapse, highlighting the need for new therapies.

B-cell maturation antigen (BCMA)-targeted CAR T-cell therapy shows promise as a new treatment option for patients with multiple myeloma who are resistant to current standard therapies, offering a different mechanism of action to combat the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cells in Multiple Myeloma Are Ready for Prime Time. Rodríguez-Otero, P., Prósper, F., Alfonso, A., et al.[2023]

The study developed novel CS1 CAR-T cells and bispecific CS1-BCMA CAR-T cells that specifically target multiple myeloma cells, showing effective tumor cell killing in laboratory tests and in live models.

These CAR-T cells not only killed multiple myeloma cells but also secreted IFN-gamma, indicating a strong immune response, and they successfully inhibited tumor growth in vivo, paving the way for future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel CS1 CAR-T Cells and Bispecific CS1-BCMA CAR-T Cells Effectively Target Multiple Myeloma. Golubovskaya, V., Zhou, H., Li, F., et al.[2021]

The study introduces bispecific CAR-T cells targeting both BCMA and CS1, which show enhanced effectiveness against multiple myeloma compared to traditional CAR-T therapies that only target BCMA.

Combining these bispecific CAR-T cells with anti-PD-1 antibodies not only improves initial tumor clearance but also leads to long-lasting tumor-free survival, suggesting a promising strategy to overcome challenges like antigen escape in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematically optimized BCMA/CS1 bispecific CAR-T cells robustly control heterogeneous multiple myeloma. Zah, E., Nam, E., Bhuvan, V., et al.[2023]

BCMA-directed therapies, such as antibody-drug conjugates and CAR T cells, have shown significant effectiveness in treating late-stage myeloma patients who have previously undergone various treatments, but the best order for using these therapies is still unclear.

After anti-BCMA therapy, there are several promising treatment options available, including alternative BCMA therapies and non-BCMA therapies, but more research is needed to personalize treatment strategies based on individual patient factors and disease characteristics.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Options at the time of relapse after anti-BCMA therapy. Razzo, B., Garfall, AL., Cohen, AD.[2023]

Citations

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kactusbio.com

kactusbio.com/blogs/news/fcrh5-an-emerging-therapeutic-target-in-multiple-myeloma?srsltid=AfmBOoqTvwpul5RGphLHCiz5uituLU-2iMGRg1vuTNZ0WvQIO9VvkWWL

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.

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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 ...

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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 ...

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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.

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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.

kactusbio.com

kactusbio.com/blogs/news/fcrh5-an-emerging-therapeutic-target-in-multiple-myeloma?srsltid=AfmBOor0Zzwy9c-ImMUV5rzDTEeAIBK4M3QqEbAM2m2mU65MacGIm-nJ

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.

7.

withpower.com

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

Cevostamab for Multiple Myeloma · Info for Participants

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 ...

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researchgate.net

researchgate.net/publication/346691841_Initial_Clinical_Activity_and_Safety_of_BFCR4350A_a_FcRH5CD3_T-Cell-Engaging_Bispecific_Antibody_in_RelapsedRefractory_Multiple_Myeloma

Initial Clinical Activity and Safety of BFCR4350A, a FcRH5 ...

OffLabel Disclosure BFCR4350A is a humanized IgG-based T-cell-engaging bispecific antibody that targets the most membrane-proximal domain of FcRH5 on myeloma ...