REGN5459 for Multiple Myeloma

No longer 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called REGN5459 (a BCMAxCD3 bispecific antibody) for individuals with multiple myeloma, a type of blood cancer, who have not succeeded with other treatments. The trial aims to determine the safety and effectiveness of REGN5459 and identify the optimal dose. It targets those whose cancer has returned or who have not responded to at least three other treatments. Participants must have undergone these treatments and still exhibit measurable signs of the disease. The trial will also assess how this treatment impacts quality of life and overall health. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that REGN5459 is likely to be safe for humans?

Research has shown that REGN5459 could be a promising treatment for multiple myeloma. Studies have found that most people tolerate it well. Early results indicate that more than 90% of patients, who have already tried many other treatments, respond positively to REGN5459. Importantly, these studies suggest that serious side effects are uncommon, indicating the treatment is generally safe.

While it's important to remember that these are early findings, they suggest that REGN5459 may work well with few serious side effects. For those considering joining a trial, these results are encouraging for safety. However, always consult a doctor to understand the possible risks and benefits. ^{1 2 3 4 5}

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

REGN5459 is unique because it targets multiple myeloma through a cutting-edge mechanism called bispecific antibody engagement. Unlike standard treatments such as proteasome inhibitors and immunomodulatory drugs, which broadly attack cancer cells, REGN5459 specifically directs the immune system to recognize and kill myeloma cells by bridging them with T-cells. This highly targeted approach has the potential to be more effective and cause fewer side effects, making researchers optimistic about its potential impact on patient outcomes.

What evidence suggests that REGN5459 might be an effective treatment for multiple myeloma?

Research has shown that REGN5459, which participants in this trial may receive, holds promise for treating relapsed or refractory multiple myeloma. In studies, patients who received the two highest doses achieved a 90.5% overall response rate, indicating that many experienced a reduction or disappearance of their cancer. This treatment is a bispecific antibody that targets two specific proteins, BCMA and CD3, to enhance the immune system's ability to attack the cancer. Early findings suggest that the responses are not only quick but also deep and lasting. Overall, the data highlight REGN5459's potential as a powerful option for patients who have tried other treatments without success. ^{1 2 4 6 7}

Who Is on the Research Team?

Clinical Trials Investigator

Principal Investigator

Regeneron Pharmaceuticals

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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 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]

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]

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]

Citations

1. aacrjournals.org aacrjournals.org/cancerres/article/83/8_Supplement/CT013/726496/Abstract-CT013-Safety-and-efficacy-from-the-phase

Abstract CT013: Safety and efficacy from the phase 1/2 first-in ... Conclusion: These initial data show that REGN5459 has acceptable safety/tolerability in R/R MM with most CRS of low grade and low incidence of ...

2. onclive.com onclive.com/view/regn5459-demonstrates-early-promise-in-heavily-pretreated-multiple-myeloma

REGN5459 Demonstrates Early Promise in Heavily ... The BCMAxCD3 bispecific antibody REGN5459 provided rapid and deep responses to heavily pretreated patients with relapsed/refractory multiple myeloma.

3. ascopost.com ascopost.com/news/april-2023/bispecific-antibody-regn5459-shows-activity-in-patients-with-relapsed-or-refractory-multiple-myeloma/

Bispecific Antibody REGN5459 Shows Activity in Patients ... Patients with relapsed or refractory multiple myeloma who received the two highest doses of REGN5459 experienced a 90.5% overall response rate, ...

4. sohoonline.org sohoonline.org/SOHO/SOHO/News/Bispecific-Antibody-Shows-Promise-in-Phase-I-II-MM-Trial.aspx

Bispecific Antibody Shows Promise in Phase I/II MM Trial REGN5459, a bispecific antibody targeting BCMA and CD3, yielded “early, durable, and deep responses” in heavily pretreated relapsed or ...

5. aacr.org aacr.org/about-the-aacr/newsroom/news-releases/new-bispecific-antibody-demonstrates-clinical-activity-in-patients-with-multiple-myeloma/

New Bispecific Antibody Demonstrates Clinical Activity in ... REGN5459, a bispecific antibody targeting BCMA and CD3, experienced a 90.5% overall response rate, according to results of a phase I/II clinical trial.

6. sciencedirect.com sciencedirect.com/science/article/pii/S0268960X25000876

Bispecific antibodies in multiple myeloma Early results show a high response rate of 91.9 % and an manageable safety profile [68]. In transplant-eligible patients, more mature data was ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8510808/

Bispecific Antibodies in Multiple Myeloma: Present and Future Bispecific antibodies are a novel immunotherapeutic modality with a favorable safety profile and impressive preliminary efficacy in heavily treated patients.