REGN5458 for Multiple Myeloma

(LINKER-MM1 Trial)

Recruiting at 88 trial locations

Overseen By Clinical Trial Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Regeneron Pharmaceuticals

Must be taking: Proteasome inhibitors, IMiDs, anti-CD38

Disqualifiers: Plasma cell leukemia, Amyloidosis, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 5 years

387 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and optimal dose of linvoseltamab (also known as REGN5458) for individuals with multiple myeloma, a type of blood cancer. Researchers aim to understand how linvoseltamab affects the body, including any side effects and its cancer-fighting capabilities. The trial includes different groups testing various doses and methods of administration. It suits those whose multiple myeloma has not responded to at least three different standard treatments, including certain drugs and therapies. 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 treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that linvoseltamab, the treatment under study, was safe in earlier studies with patients who have relapsed or hard-to-treat multiple myeloma. These studies found that many patients responded well, with lasting improvements. While some side effects occurred, they were generally manageable. Importantly, few serious infections were reported, resulting in fewer severe problems for patients. Overall, the treatment appears well-tolerated, but this trial aims to learn more about the optimal dose and side effects. ^{1 2 3 4 5}

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

Unlike the standard treatments for multiple myeloma, which often include combinations of chemotherapy, steroids, and other targeted therapies, Linvoseltamab is unique because it employs a novel approach. This investigational drug is a bispecific antibody that targets both BCMA (B-cell maturation antigen) on myeloma cells and CD3 on T-cells, essentially recruiting the body's immune system to directly attack the cancer cells. Additionally, researchers are exploring different delivery methods and dosages, including intravenous and subcutaneous options, which could offer more flexibility and potentially improve patient convenience and outcomes. This targeted action and innovative administration make Linvoseltamab a promising candidate that could change the treatment landscape for multiple myeloma.

What evidence suggests that linvoseltamab could be an effective treatment for multiple myeloma?

Research has shown that linvoseltamab, which participants in this trial may receive, may effectively treat multiple myeloma, a type of blood cancer. Studies have found that about 51% of patients responded positively to the treatment, with about half showing improvement. In one study, patients who received a 50 mg dose had a 48.1% response rate, with many experiencing significant improvement. Another study found even better results in patients with high-risk multiple myeloma, suggesting it could be particularly effective for them. Overall, linvoseltamab shows promising results for people with relapsed or difficult-to-treat multiple myeloma. ^{1 2 4 6 7}

Who Is on the Research Team?

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Are You a Good Fit for This Trial?

This trial is for adults with Multiple Myeloma who've tried at least three prior treatments, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody but haven't seen improvement. They should be in relatively good health otherwise (ECOG ≤ 1). People can't join if they have certain other blood disorders or brain involvement of myeloma, severe heart issues, previous BCMA-targeted therapy except antibody-drug conjugates, or recent stem cell transplants.

Inclusion Criteria

My myeloma can be measured for treatment response.

I have been diagnosed with active Multiple Myeloma.

I have multiple myeloma and no remaining treatment options that could significantly help me.

Exclusion Criteria

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

My heart's pumping ability is less than 40%.

I have brain lesions or meningeal involvement due to multiple myeloma.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Phase 1 involves dose escalation and subcutaneous administration of REGN5458; Phase 2 involves low and high dose IV monotherapy

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• REGN5458

Trial Overview The study tests REGN5458 as a solo treatment to see how safe it is and what dose works best (Phase 1), then checks its effectiveness against Multiple Myeloma that's resisted standard treatments (Phase 2). Researchers will also look into how the body processes the drug and any potential impact on quality of life.

How Is the Trial Designed?

Group I: Linvoseltamab - Phase 2 - Cohort 3 Experimental Treatment 1 Intervention

Anti-interleukin (IL)-6 receptor (R) prophylactic therapy followed by high dose of IV linvoseltamab monotherapy Note: Cohort 3 is not applicable for US.

Group II: Linvoseltamab - Phase 2 - Cohort 2 Experimental Treatment 1 Intervention

High Dose of linvoseltamab IV monotherapy.

Group III: Linvoseltamab - Phase 2 - Cohort 1 Experimental Treatment 1 Intervention

Low Dose of linvoseltamab IV monotherapy.

Group IV: Linvoseltamab - Phase 1 Experimental Treatment 1 Intervention

Phase 1 has two parts. Part 1, consists of linvoseltamab intravenous (IV) dose escalation and Part 2, consists of subcutaneous (SC) administration. Note: subcutaneous (SC) administration is not applicable for US.

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

Citations

1. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/7012/527741/Comparative-Effectiveness-of-Linvoseltamab-Versus

Comparative Effectiveness of Linvoseltamab Versus Current ... High objective response rates (ORR) to linvoseltamab 200 mg in the LINKER-MM1 trial (NCT03761108) were demonstrated across high-risk subgroups, ...

2. onclive.com onclive.com/view/linvoseltamab-adds-highly-effective-option-in-later-line-multiple-myeloma

Linvoseltamab Adds Highly Effective Option in Later-Line ... Data from LINKER-MM1 revealed that patients who received the BCMA-directed CD3 T-cell engager (n = 80) experienced an objective response rate ( ...

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.24.01008

Linvoseltamab for Treatment of Relapsed/Refractory ... Patients treated with 50 mg linvoseltamab had an ORR of 48.1%, with 39.4% of patients achieving ≥VGPR and 21.2% of patients achieving ≥CR (Fig ...

4. investor.regeneron.com investor.regeneron.com/news-releases/news-release-details/new-regn5458-bcmaxcd3-phase-1-data-show-75-response-rate-highest/

New REGN5458 (BCMAxCD3) Phase 1 Data Show 75% ... The new results from the Phase 1 portion of the Phase 1/2 trial in patients with relapsed/refractory multiple myeloma found a 51% overall response rate (ORR) ...

5. onclive.com onclive.com/view/linvoseltamab-demonstrates-potential-for-early-intervention-in-high-risk-smoldering-multiple-myeloma

Linvoseltamab Demonstrates Potential for Early ... The efficacy of linvoseltamab in this population is quite remarkable. We have 19 out of the 24 patients that are evaluable for response, and the ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/3369/532700/Linvoseltamab-in-Patients-with-Relapsed-Refractory

Linvoseltamab in Patients with Relapsed/Refractory Multiple ... Linvoseltamab induced deep and durable responses with an acceptable safety profile in patients with relapsed/refractory multiple myeloma (RRMM) ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38879802/

Linvoseltamab for Treatment of Relapsed/Refractory ... Linvoseltamab 200 mg induced deep and durable responses, with a median DOR of 29.4 months, in patients with RRMM with an acceptable safety profile.