Cevostamab for Multiple Myeloma

Recruiting at 20 trial locations

Overseen By Reference Study ID Number: GO39775 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, HIV, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 21-day cycles, up to approximately 8 years

420 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing cevostamab, a medication given through an IV drip, in patients with multiple myeloma that has returned or didn't respond to other treatments. The drug helps the immune system kill cancer cells. Cevostamab is currently under investigation for its potential to treat multiple myeloma.

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

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had certain treatments like monoclonal antibodies, systemic immunotherapeutic agents, or chemotherapeutic agents within specific time frames before the first infusion. It's best to discuss your current medications with the trial team.

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 have had certain cancer treatments or immunosuppressive medications recently, so it's best to discuss your specific medications with the study team.

What data supports the idea that Cevostamab for Multiple Myeloma is an effective treatment?

The available research shows that Cevostamab, also known as the anti-FcRH5/CD3 bispecific antibody, is effective in treating multiple myeloma. It works by targeting specific markers on myeloma cells, leading to their destruction. In studies, it has been shown to kill myeloma cells at very low concentrations and completely remove certain types of cells in animal models. This suggests that Cevostamab has strong potential as a treatment for multiple myeloma. Compared to other treatments like teclistamab, which has a response rate of 64%, Cevostamab's ability to target and kill myeloma cells efficiently highlights its promise as an effective option. ^{1 2 3 4 5}

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, suggesting its potential in treating multiple myeloma. Additionally, similar bispecific antibodies have shown high response rates in early clinical trials for multiple myeloma, indicating promise for this type of treatment. ^{1 2 3 4 5}

What safety data exists for Cevostamab in treating multiple myeloma?

The safety data for Cevostamab, also known as anti-FcRH5/CD3 T-cell dependent bispecific antibody, includes findings from preclinical studies and early-phase clinical trials. Preclinical studies demonstrated its ability to kill myeloma cells and deplete B cells in cynomolgus monkeys. In clinical settings, similar to other bispecific antibodies, adverse events of interest include cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, with incidence rates ranging from approximately 40% to 90% and 3% to 20%, respectively. These findings highlight the potential and safety considerations of Cevostamab in treating multiple myeloma. ^{1 2 6 7 8}

What safety data exists for Cevostamab in humans?

Cevostamab, also known as anti-FcRH5/CD3, has been studied for its ability to target and kill myeloma cells, but it can cause 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). These side effects have been observed in a significant number of patients, ranging from 40% to 90% for cytokine release syndrome and 3% to 20% for neurotoxicity. ^{1 2 6 7 8}

Is the drug Cevostamab a promising treatment for Multiple Myeloma?

Yes, Cevostamab is a promising drug for Multiple Myeloma. It targets specific markers on cancer cells, helping the immune system to attack and kill these cells effectively. It has shown strong potential in early studies, even at very low doses, and could be used alone or with other treatments to fight this type of cancer. ^{1 2 4 6 9}

How is the drug Cevostamab unique in treating multiple myeloma?

Cevostamab is unique because it is a bispecific antibody that targets the FcRH5 marker on multiple myeloma cells and CD3 on T cells, facilitating the formation of a synapse that activates T cells to kill myeloma cells. This mechanism allows it to effectively deplete B cells and bone marrow plasma cells, offering a novel approach compared to other treatments. ^{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, are not pregnant or breastfeeding, and can perform daily activities with minimal assistance. They must not have had certain recent treatments, transplants, major surgeries, infections including COVID-19 within specific time frames, a history of severe allergies to monoclonal antibodies, or any condition that could interfere with the study.

Inclusion Criteria

You have a disease that can be measured with lab tests.

I agree not to donate sperm and to use contraception during and for 2 months after treatment.

You are expected to live for at least 12 more weeks.

Exclusion Criteria

I have or might have a long-term EBV infection or hepatitis C.

I have not had major surgery in the last 4 weeks.

I haven't had any antibody-based cancer treatments in the last 4 weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive cevostamab in a dose-escalation study with various dosing schedules across different arms

21-day cycles, up to approximately 8 years

Multiple visits per cycle for dose administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 8 years

Treatment Details

Interventions

• Cevostamab

Trial Overview The study tests different doses of Cevostamab given through IV infusion to see how safe it is and how well it works in treating multiple myeloma that has come back or hasn't responded to treatment. Tocilizumab may also be used if needed. It's an early-phase trial where researchers closely monitor participants' reactions.

Participant Groups

Group I: Arm K: Compressed Double Step Dose Expansion for Cevostamab Experimental Treatment 1 Intervention

In Cycle 1, participants will receive 2 step-up doses and a target dose. The doses will be given on Cycle 1 Days 1, 4, and 8. Subsequently the target dose will be administered on Day 1 of each 21-day cycle.

Group II: Arm J: Expansion Phase for Tocilizumab Pretreatment Experimental Treatment 2 Interventions

All participants will receive a single dose of tocilizumab intravenously. An additional dose of tocilizumab may be instituted as premedication for subsequent Cycle 1 dose(s) of cevostamab and Cycle 1 cevostamab doses for other treatment arms.

Group III: Arm I: Triple Step Dose Expansion for Cevostamab Experimental Treatment 1 Intervention

The triple step dose expansion stage of the study may use the dosing and assessment schedule from the triple step dose escalation arm in Cycle 1, based on data from Arm H.

Group IV: Arm H: Triple Step Dose Escalation for Cevostamab Experimental Treatment 1 Intervention

In Cycle 1, participants will receive 3 step-up doses and a target dose. The doses will be given on Cycle 1 Days 1, 2-4, 8, and 9-11. Subsequently the target dose will be administered on Day 1 of each 21-day cycle.

Group V: Arm G: Double Step Dose Expansion for Cevostamab Experimental Treatment 1 Intervention

The double step dose expansion stage of the study may use the dosing and assessment schedule from the double step dose escalation arm in Cycle 1, based on data from Arm B.

Group VI: Arm F: Single Step Dose Expansion for Cevostamab Experimental Treatment 1 Intervention

The single step dose expansion stage of the study may use the dosing and assessment schedule from the single dose escalation arm in Cycle 1, based on data from Arm A.

Group VII: Arm E: Expansion Phase for Tocilizumab Pretreatment Experimental Treatment 2 Interventions

All participants will receive a single dose of tocilizumab intravenously. An additional dose of tocilizumab may be instituted as premedication for subsequent Cycle 1 dose(s) of cevostamab and Cycle 1 cevostamab doses for other treatment arms.

Group VIII: Arm D: Double Step Dose Expansion for Cevostamab Experimental Treatment 1 Intervention

The double step dose expansion stage of the study may use the dosing and assessment schedule from the double step dose escalation arm in Cycle 1, based on data from Arm B.

Group IX: Arm C: Single Step Dose Expansion for Cevostamab Experimental Treatment 1 Intervention

The single step dose expansion stage of the study may use the dosing and assessment schedule from the single dose escalation arm in Cycle 1, based on data from Arm A.

Group X: Arm B: Double Step Dose Escalation for Cevostamab Experimental Treatment 1 Intervention

In Cycle 1, participants will receive 2 step-up doses and a target dose. The step-up dose will be given on Cycle 1 Day 1 and C1D8. The target dose will be given on C1D15. Subsequently the target dose will be administered on Day 1 of each 21-day cycle.

Group XI: Arm A: Single Step Dose Escalation for Cevostamab Experimental Treatment 1 Intervention

Study drug will be administered intravenously on a 21-day cycle. The step-up dose will be given on Cycle 1 Day 1 and the target dose will be given on C1D8. Subsequently the target dose will be administered on Day 1 of each 21-day cycle.

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

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]

SAR442085, a next-generation anti-CD38 monoclonal antibody, demonstrated superior binding affinity and enhanced antibody-dependent cellular cytotoxicity (ADCC) compared to first-generation antibodies like daratumumab and isatuximab in preclinical studies involving multiple myeloma cells.

In vivo studies using transgenic mice showed that SAR442085 resulted in better natural killer (NK) cell activation and improved antitumor efficacy, leading to increased survival rates compared to existing anti-CD38 therapies, supporting its potential for clinical evaluation in patients with relapsed/refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

SAR442085, a novel anti-CD38 antibody with enhanced antitumor activity against multiple myeloma. Kassem, S., Diallo, BK., El-Murr, N., 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]

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

SAR442085, a novel anti-CD38 antibody with enhanced antitumor activity against multiple myeloma. [2022]

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]