REGN5459 for Multiple Myeloma

Recruiting at 6 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Regeneron Pharmaceuticals

Must not be taking: Anti-BCMA, BCMA-directed CAR T

Disqualifiers: MM brain lesions, Neurodegenerative condition, Cardiac ejection fraction <40%, Uncontrolled infection, others

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

Compensation: Varies

Number of Visits: Unknown

43 Participants Needed

Trial Summary

Do I need to stop my current medications to join the trial?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor to get a clear answer.

What data supports the effectiveness of the drug REGN5459 for treating multiple myeloma?

Research shows that BCMA-targeting bispecific antibodies, like REGN5459, are effective in killing myeloma cells by directing immune cells to attack them. These antibodies have shown promising results in reducing tumor size and improving outcomes in multiple myeloma patients. ^{1 2 3 4 5}

Is REGN5459 safe for humans?

REGN5459, also known as BCMAxCD3 bispecific antibody, has been tested in clinical trials for multiple myeloma and has shown a good safety profile. Common side effects include cytokine release syndrome (a reaction that can cause fever and low blood pressure), anemia (low red blood cell count), neutropenia (low white blood cell count), and thrombocytopenia (low platelet count). ^{1 5 6 7 8}

How is the drug REGN5459 unique in treating multiple myeloma?

REGN5459 is a bispecific antibody that targets both BCMA on myeloma cells and CD3 on T cells, helping the immune system directly attack the cancer. This approach allows for rapid tumor clearance by engaging T cells already present at the tumor site, unlike CAR T-cell therapies that require time to activate and expand. ^{1 3 5 8 9}

What is the purpose of this trial?

In the phase 1 portion of the study, the primary objectives are to assess the safety, tolerability, and dose-limiting toxicities (DLTs) and to determine a recommended phase 2 dose regimen (RP2DR) of REGN5459 as monotherapy in patients with relapsed or refractory multiple myeloma (MM) who have exhausted all therapeutic options that are expected to provide meaningful clinical benefit. In the phase 2 portion of the study, the primary objective is to assess the preliminary anti-tumor activity of REGN5459 as measured by objective response rate (ORR). In the phase 1 and phase 2 portion, the secondary objectives of the study are: * To assess the preliminary anti-tumor activity of REGN5459 as measured by duration of response (DOR), progression-free survival (PFS), rate of minimal residual disease (MRD) negative status, and overall survival (OS) * To evaluate the pharmacokinetic (PK) properties of REGN5459 * To characterize the immunogenicity of REGN5459 * To evaluate the effects of REGN5459 on patient-reported quality of life (QoL), symptoms, functioning and general health status In the phase 1 portion of the study only, the secondary objective of the study is to assess the preliminary anti-tumor activity of REGN5459 as measured by ORR. In the phase 2 portion of the study only, the secondary objective of the study is to evaluate the safety and tolerability of REGN5459.

Research Team

Clinical Trials Investigator

Principal Investigator

Regeneron Pharmaceuticals

Eligibility Criteria

Adults with relapsed or refractory Multiple Myeloma who have tried at least three lines of therapy, including a proteasome inhibitor, an IMiD, and an anti-CD38 antibody. They should not have brain involvement by MM or certain neurological conditions, no recent seizures, adequate heart function, and no prior BCMA-targeted therapies. Patients must also be free from uncontrolled infections like HIV or hepatitis.

Inclusion Criteria

My kidney function, measured by creatinine clearance, is above 30 mL/min.

I've had 3 types of treatments for my condition and they didn't work or I couldn't tolerate them.

You are expected to live for at least 6 more months.

Exclusion Criteria

Your heart's pumping ability is less than 40% according to a heart imaging test.

I have had a stem cell transplant from a donor or my own within the past 12 weeks.

I have not had treatments targeting BCMA for my cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase 1 Treatment

Participants receive REGN5459 to assess safety, tolerability, and dose-limiting toxicities

Up to 35 days

Phase 2 Treatment

Participants receive REGN5459 to assess preliminary anti-tumor activity

Up to 104 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks after the last dose

Treatment Details

Interventions

• REGN5459

Trial Overview The trial is testing REGN5459 as a solo treatment for Multiple Myeloma in two phases: Phase 1 to find the safest dose with acceptable side effects (dose-limiting toxicities) and Phase 2 to see how well it works against cancer (measuring response rate). The study will also look at how long the benefits last and any impacts on quality of life.

Participant Groups

Group I: REGN5459 Experimental Treatment 1 Intervention

Cohorts of multiple REGN5459 dose levels

Who Is Running the Clinical Trial?

Regeneron Pharmaceuticals

Lead Sponsor

Trials

690

Recruited

948,000+

Founded

1988

Headquarters

Tarrytown, USA

Known For

Precision medicine

Top Products

Dupixent, EYLEA, Libtayo, Praluent

Leonard Schleifer

Regeneron Pharmaceuticals

Chief Executive Officer since 1988

MD and PhD in Medicine

George Yancopoulos

Regeneron Pharmaceuticals

Chief Medical Officer since 1997

MD from Harvard Medical School

Findings from Research

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]

The bispecific antibody 2A9-MICA effectively targets malignant plasma cells in multiple myeloma by combining the MICA protein, which activates immune cells, with a fragment that specifically binds to BCMA, enhancing immune response against the cancer.

In preclinical studies with BCMA-positive mice, 2A9-MICA demonstrated significant tumor growth inhibition and improved recruitment of immune cells to the tumor site, suggesting its potential as a promising immunotherapy for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BCMA-targeting Bispecific Antibody That Simultaneously Stimulates NKG2D-enhanced Efficacy Against Multiple Myeloma. Wang, Y., Li, H., Xu, W., et al.[2021]

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]

A study compared the efficacy of a CD3 bispecific antibody and two types of antibody-drug conjugates (ADCs) targeting B-cell maturation antigen (BCMA) in treating myeloma, showing that both modalities effectively killed myeloma cells in vitro and in vivo.

The CD3 bispecific antibody demonstrated superior potency and consistency in killing primary patient cells compared to ADCs, leading to its advancement into phase I clinical trials due to its better efficacy and improved toxicity profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Efficacy and Safety Comparison of CD3 Bispecific and ADC Modalities Targeting BCMA for the Treatment of Multiple Myeloma. Panowski, SH., Kuo, TC., Zhang, Y., et al.[2020]

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]

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]

The fully human bispecific antibody REGN5458, which targets B-cell maturation antigen (BCMA) and CD3, effectively induces T-cell killing of multiple myeloma cells and shows strong antitumor activity in mouse models, demonstrating its potential as a rapid therapeutic option.

In head-to-head comparisons, REGN5458 cleared tumors more quickly than anti-BCMA CAR T cells, suggesting that bispecific antibodies can engage existing T cells at the tumor site for immediate action, while CAR T cells require time to activate and expand before they can attack the tumor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A BCMAxCD3 bispecific T cell-engaging antibody demonstrates robust antitumor efficacy similar to that of anti-BCMA CAR T cells. DiLillo, DJ., Olson, K., Mohrs, K., et al.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Newly approved and forthcoming T-cell-redirecting bispecific antibodies for the treatment of relapsed/refractory multiple myeloma. [2023]

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

BCMA-targeting Bispecific Antibody That Simultaneously Stimulates NKG2D-enhanced Efficacy Against Multiple Myeloma. [2021]

3. 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]

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

Preclinical Efficacy and Safety Comparison of CD3 Bispecific and ADC Modalities Targeting BCMA for the Treatment of Multiple Myeloma. [2020]

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

Tumor burden limits bispecific antibody efficacy through T cell exhaustion averted by concurrent cytotoxic therapy. [2022]

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

The Role of Bispecific Antibodies in Relapsed Refractory Multiple Myeloma: A Systematic Review. [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

Bispecific Antibodies in Multiple Myeloma: Present and Future. [2023]

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

A BCMAxCD3 bispecific T cell-engaging antibody demonstrates robust antitumor efficacy similar to that of anti-BCMA CAR T cells. [2021]