Cevostamab for Multiple Myeloma

(CAMMA 1 Trial)

Recruiting at 51 trial locations

Overseen By Reference Study ID Number: GO42552 https://forpatients.roche.com/

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Genentech, Inc.

Must not be taking: Monoclonal antibodies, Immunotherapeutics

Disqualifiers: Pregnancy, Autoimmune disease, Cardiovascular, CNS disease, others

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

Compensation: Varies

Number of Visits: 2

Duration: 8-12 months

126 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called cevostamab alone and with other drugs to help patients with multiple myeloma that has come back or not responded to treatment. The drug aims to help the immune system kill cancer cells.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, it does mention that you should not have had certain treatments like monoclonal antibodies or chemotherapy within a few weeks before starting the trial. It's best to discuss your specific medications with the trial 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, indicating its potential for treating multiple myeloma. Additionally, similar bispecific antibodies have shown high response rates in early clinical trials for multiple myeloma, suggesting that Cevostamab may also be effective. ^{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 studies, it has shown potential for treating multiple myeloma, but like other similar treatments, it may cause side effects such as 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). ^{1 2 6 7 8}

How is the drug Cevostamab unique in treating 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 to attack the cancer cells. This mechanism is different from other treatments that may target different proteins or use different methods to engage the immune system. ^{1 2 4 6 9}

Research Team

Clinical Trials

Principal Investigator

Genentech, Inc.

Eligibility Criteria

This trial is for adults with relapsed or refractory Multiple Myeloma who have tried other treatments without success or cannot tolerate them. Participants must be willing to provide bone marrow samples, use contraception, and have a life expectancy of at least 12 weeks. They should not have had certain recent treatments, autoimmune diseases, major surgery, severe heart conditions, or specific allergies.

Inclusion Criteria

My multiple myeloma has returned or is resistant, and I can't tolerate or use standard treatments.

You have a disease that can be measured or seen on tests or scans.

I agree to use contraception or remain abstinent and not donate sperm or blood while on pomalidomide and for 4 weeks after.

Exclusion Criteria

I have had a stem cell transplant from a donor.

I haven't taken strong immune-suppressing drugs, except for low-dose steroids, in the last 2 weeks.

I need extra oxygen or have trouble breathing due to lung problems.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cevostamab monotherapy or cevostamab in combination with pomalidomide and dexamethasone or daratumumab and dexamethasone. Treatment is administered in cycles with varying schedules depending on the arm.

8-12 months

Visits every 2-4 weeks depending on the treatment arm

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 Cevostamab alone or combined with Pomalidomide and Dexamethasone (Pd) or Daratumumab and Dexamethasone (Dd). It's an open-label Phase Ib trial where participants receive these drugs through IV infusion to assess safety, tolerability, how the body processes the drug (PK), and how it works in the body (PD).

Participant Groups

Group I: Single-Agent Cevostamab (Arm A) Experimental Treatment 3 Interventions

Cohort A1S is a safety run-in arm evaluating cevostamab administered in 28-day cycles on a modified weekly schedule. Cohort A1E, an expansion cohort, has been opened and finished enrolling participants. Participants will be treated with single-agent cevostamab administered in 28-day cycles on a modified weekly schedule.

Group II: Cevostamab plus Pomalidomide and Dexamethasone (Pd) (Arm B) Experimental Treatment 4 Interventions

Participants will be treated with cevostamab monotherapy during a 14-day period prior to the start of pomalidomide treatment (cevostamab pre-phase). Cohort B1S is a safety run-in arm evaluating cevostamab and Pd administered in 28-day cycles every 2 weeks (Q2W) followed by every 4 weeks (Q4W) schedule. Additional safety run-in cohort(s) with lower target dose levels of cevostamab may be opened prior to opening the expansion cohorts. Two target dose levels of target dose level 1 (DL1) and lower dose level -1 (DL-1) of cevostamab will be selected for randomization in expansion cohorts. Expansion cohorts will follow the same Q2W/Q4W dosing schedule as Cohort B1S.

Group III: Cevostamab plus Daratumumab and Dexamethasone (Dd) (Arm C) Experimental Treatment 4 Interventions

Cohort C1S is a safety run-in arm evaluating cevostamab and Dd administered in 21 day cycles from Cycle(C)1 - C8 every 3 weeks (Q3W) and 28-day cycles from C9 onwards Q4W. Additional safety run-in cohort(s) with lower target dose levels of cevostamab may be opened prior to opening the expansion cohorts. Two target dose levels of DL1 and DL-1 of cevostamab will be selected for randomization in expansion cohorts. Expansion cohorts will follow the same Q3W/Q4W dosing schedule as Cohort C1S.

Who Is Running the Clinical Trial?

Genentech, Inc.

Lead 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

Hoffmann-La Roche

Industry 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 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]

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]

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

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

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

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

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

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

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

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

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

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