Cevostamab Following CAR T Cell Therapy for Multiple Myeloma

Overseen by Adam D Cohen, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial tests Cevostamab, an IV medication given periodically, in patients with myeloma that has returned or not responded to treatment. These patients have already received a special cell therapy and are recovering from it. The goal is to see if Cevostamab can help their immune system better fight the cancer.

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.

What data supports the effectiveness of the treatment Cevostamab for multiple myeloma?

The research highlights the effectiveness of bispecific antibodies, like Cevostamab, in targeting multiple myeloma by redirecting T cells to attack cancer cells. Similar treatments have shown promising results in clinical trials, suggesting that Cevostamab could be a valuable option for patients who have already undergone CAR T cell therapy. ^{1 2 3 4 5}

How is the treatment Cevostamab unique for multiple myeloma?

Cevostamab is unique because it is a bispecific antibody that targets B-cell maturation antigen (BCMA), redirecting T cells to attack multiple myeloma cells. This approach is different from traditional therapies as it specifically engages the immune system to target cancer cells, offering a novel mechanism of action for patients who have relapsed after other treatments like CAR T-cell therapy. ^{1 2 3 6 7}

Research Team

Adam D Cohen, MD

Principal Investigator

University of Pennsylvania

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Cevostamab (Monoclonal Antibodies)

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.

Participant Groups

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+

Dr. Joan Lau

University of Pennsylvania

Chief Executive Officer since 2020

PhD in Neuroscience from the University of Cincinnati College of Medicine, MBA from the Wharton School of Business, BS in Bioengineering from the University of Pennsylvania

Dr. Robert Iannone

University of Pennsylvania

Chief Medical Officer since 2019

MD from Yale University, MSCE from the University of Pennsylvania

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

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]

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]

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]

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]

References

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

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

2. England pubmed.ncbi.nlm.nih.gov

Systematically optimized BCMA/CS1 bispecific CAR-T cells robustly control heterogeneous multiple myeloma. [2023]

3. Switzerland pubmed.ncbi.nlm.nih.gov

CAR T-Cells in Multiple Myeloma Are Ready for Prime Time. [2023]

4. United States 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. [2023]

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

Options at the time of relapse after anti-BCMA therapy. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Novel CS1 CAR-T Cells and Bispecific CS1-BCMA CAR-T Cells Effectively Target Multiple Myeloma. [2021]

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

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