Linvoseltamab vs EPd for Multiple Myeloma

(LINKER-MM3 Trial)

Recruiting at 275 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Regeneron Pharmaceuticals

Must not be taking: Elotuzumab, Pomalidomide, BCMA immunotherapies

Disqualifiers: Plasma cell leukemia, Amyloidosis, Waldenström macroglobulinemia, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

410 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, linvoseltamab, to evaluate its effectiveness for people with multiple myeloma, a type of blood cancer, compared to a combination of three other drugs: elotuzumab, pomalidomide, and dexamethasone. The research aims to determine if linvoseltamab can improve symptoms and outcomes for those whose cancer has returned after one to four previous treatments. Participants will receive either linvoseltamab or the three-drug combination to compare their effects. Individuals with multiple myeloma that has returned or not responded well to past treatments might be suitable candidates, especially if they have previously tried lenalidomide and a proteasome inhibitor. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that you cannot have had any systemic anti-cancer therapy within 28 days before starting the study drug. It's best to discuss your current medications with the study team.

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

Research has shown that linvoseltamab has promising safety results from earlier studies. In patients with relapsed or hard-to-treat multiple myeloma, linvoseltamab was generally well-tolerated. Some participants experienced tumor shrinkage, and a few had complete responses where all signs of myeloma disappeared. The treatment had manageable side effects, meaning they were present but could be controlled. Importantly, no new safety concerns emerged during follow-up.

The EPd combination (elotuzumab, pomalidomide, and dexamethasone) is already used to treat multiple myeloma, so its safety is well-known and generally accepted. However, every treatment can have side effects, which can vary from person to person. Participants should discuss potential side effects with their healthcare provider before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Linvoseltamab is unique because it works differently from standard multiple myeloma treatments by targeting BCMA (B-cell maturation antigen) on the surface of myeloma cells. This targeted approach allows it to directly attack cancer cells more effectively. Researchers are excited about Linvoseltamab because its novel mechanism could lead to better outcomes for patients who haven't responded well to other therapies like those involving Elotuzumab, Pomalidomide, and Dexamethasone. This could be a game-changer for patients with limited treatment options.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research shows that linvoseltamab, one of the treatments tested in this trial for multiple myeloma, has promising results. In earlier studies, patients with advanced multiple myeloma who had tried many other treatments saw their tumors shrink with linvoseltamab. Some patients even experienced complete responses, with no signs of cancer remaining. The response rate reached 75% at the highest doses, and some patients remained cancer-free for an average of 29.4 months. These findings suggest that linvoseltamab could be a strong option for patients whose multiple myeloma has returned or is difficult to treat. Another treatment arm in this trial involves the combination of Elotuzumab, Pomalidomide, and Dexamethasone (EPd), serving as an active comparator. ^{1 2 3 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 people with multiple myeloma that's come back or needs more treatment after 1-4 previous therapies. They must have measurable disease, be mostly active (ECOG ≤1), and have used lenalidomide and a proteasome inhibitor before. Their blood, liver, kidneys, heart, and bone marrow should work well enough to handle the treatments.

Inclusion Criteria

I've had 1-4 treatments for my MM, including specific drugs, and my disease has progressed.

Life expectancy of at least 6 months

My blood, liver, kidneys, heart, and bone marrow are functioning well.

Exclusion Criteria

I have had BCMA-targeted therapy, but BCMA antibody-drug conjugates are okay.

I had a stem cell transplant recently and am not on strong immune-suppressing drugs.

I do not have an uncontrolled infection like HIV, HBV, or HCV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either linvoseltamab or the combination of elotuzumab, pomalidomide, and dexamethasone (EPd)

12 weeks

Regular visits as per treatment protocol

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dexamethasone
• Elotuzumab
• Linvoseltamab
• Pomalidomide

Trial Overview The study compares linvoseltamab (REGN5458) with a standard combo of cancer drugs: elotuzumab, pomalidomide & dexamethasone (EPd). Participants are split into two groups; one gets linvoseltamab while the other receives EPd. The goal is to see which group does better in terms of safety, effectiveness, side effects duration of benefit and overall survival.

How Is the Trial Designed?

Group I: Linvoseltamab Experimental Treatment 1 Intervention

Randomization 1:1

Group II: Elotuzumab/Pomalidomide/Dexamethasone (EPd) Active Control 3 Interventions

Randomization 1:1

Dexamethasone is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases
• Immune system disorders

Approved in United States as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders
• Neoplastic diseases
• Nervous system disorders

Approved in Canada as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases

Approved in Japan as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders

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

Pomalidomide, when combined with low-dose dexamethasone, significantly improves progression-free survival and overall survival in adults with relapsed and refractory multiple myeloma, based on results from multinational phase II and III studies involving patients who had undergone at least two prior treatments.

The treatment has a manageable safety profile, with the most common serious side effects being neutropenia, infections, anemia, and thrombocytopenia, making it a viable option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide: A Review in Relapsed and Refractory Multiple Myeloma. Hoy, SM.[2018]

In a study of 117 patients with relapsed or refractory multiple myeloma, those treated with elotuzumab plus pomalidomide and dexamethasone experienced a median progression-free survival of 10.3 months, compared to 4.7 months for those receiving pomalidomide and dexamethasone alone, indicating a significant improvement in treatment efficacy.

The overall response rate was also higher in the elotuzumab group at 53% versus 26% in the control group, with fewer severe adverse events like neutropenia and anemia, suggesting that elotuzumab may enhance treatment outcomes while maintaining a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma. Dimopoulos, MA., Dytfeld, D., Grosicki, S., et al.[2019]

Elotuzumab, a monoclonal antibody targeting the SLAMF7 receptor, shows no significant activity as a standalone treatment for relapsed or refractory multiple myeloma, but improves outcomes when combined with other therapies like lenalidomide and dexamethasone.

The FDA approved elotuzumab in November 2015 for multiple myeloma patients who have undergone one to three prior treatments, based on positive results from the ELOQUENT-2 phase III clinical trial, highlighting its efficacy in combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab: the first approved monoclonal antibody for multiple myeloma treatment. Magen, H., Muchtar, E.[2020]

Elotuzumab combined with pomalidomide and dexamethasone (E-Pd) was shown to effectively prolong progression-free survival (PFS) in patients with relapsed and refractory multiple myeloma (RRMM), based on data from 440 patients in the ELOQUENT-3 study.

The pharmacokinetics of elotuzumab were well-characterized, revealing that its exposure did not lead to an increase in severe adverse events (grade 3+ AEs), indicating a favorable safety profile when used with the Pd regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population pharmacokinetic and exposure-response analyses of elotuzumab plus pomalidomide and dexamethasone for relapsed and refractory multiple myeloma. Ide, T., Osawa, M., Sanghavi, K., et al.[2022]

In a myeloma mouse model, combining tumor antigen-loaded dendritic cells with pomalidomide and dexamethasone significantly inhibited tumor growth compared to other treatment groups, indicating enhanced antitumor immunity.

This combination therapy reduced immune suppressor cells and increased immune effector cells, suggesting a shift from an immune-suppressive to an immune-supportive environment, which could improve treatment outcomes in myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Synergistic Antimyeloma Activity of Dendritic Cells and Pomalidomide in a Murine Myeloma Model. Vo, MC., Yang, S., Jung, SH., et al.[2019]

In the phase II ELOQUENT-3 trial, the combination of elotuzumab with pomalidomide and dexamethasone (EPd) significantly improved overall survival (OS) in patients with relapsed/refractory multiple myeloma, with a median OS of 29.8 months compared to 17.4 months for the pomalidomide/dexamethasone (Pd) group.

The safety profile of EPd was consistent with previous studies, showing no new safety concerns, indicating that this treatment is both effective and safe for patients who have already undergone multiple lines of therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab Plus Pomalidomide and Dexamethasone for Relapsed/Refractory Multiple Myeloma: Final Overall Survival Analysis From the Randomized Phase II ELOQUENT-3 Trial. Dimopoulos, MA., Dytfeld, D., Grosicki, S., et al.[2023]

In the phase III ELOQUENT-2 trial involving adults with relapsed multiple myeloma, elotuzumab combined with lenalidomide and dexamethasone significantly improved progression-free survival and overall response rates compared to the standard treatment alone.

The addition of elotuzumab did not negatively affect health-related quality of life and had a manageable safety profile, with the most common serious side effects being blood-related issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab: A Review in Relapsed and/or Refractory Multiple Myeloma. Lamb, YN.[2019]

The combination of elotuzumab with pomalidomide and dexamethasone has shown promising efficacy in treating refractory or relapsed multiple myeloma, suggesting it may be more effective than the standard pomalidomide and dexamethasone regimen alone.

As most multiple myeloma patients will likely receive initial treatments with proteasome inhibitors and lenalidomide, the elotuzumab-pomalidomide-dexamethasone combination is expected to become the standard second-line therapy for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab in combination with pomalidomide and dexamethasone for the treatment of multiple myeloma. Eleutherakis-Papaiakovou, E., Gavriatopoulou, M., Ntanasis-Stathopoulos, I., et al.[2020]

In a study of 103 patients with relapsed/refractory multiple myeloma, the combination of daratumumab, pomalidomide, and dexamethasone showed an overall response rate of 60%, indicating significant efficacy even in patients with a history of multiple prior therapies.

The safety profile of this combination treatment was similar to pomalidomide and dexamethasone alone, with the main exception being a higher incidence of neutropenia and infusion-related reactions, but without an increase in infection rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Chari, A., Suvannasankha, A., Fay, JW., et al.[2022]

Citations

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

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

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

Comparative Effectiveness of Linvoseltamab Versus Current ... Linvoseltamab, an investigational BCMAxCD3 bispecific antibody, for the treatment of patients with relapsed or refractory multiple myeloma.

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

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.

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% ... New REGN5458 (BCMAxCD3) Phase 1 Data Show 75% Response Rate at Highest Dose Levels Studied in Patients with Heavily Pretreated Multiple Myeloma.

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

Linvoseltamab Adds Highly Effective Option in Later-Line ... Patients also had stringent CRs (39%), CRs (6%), very good partial responses (VGPRs; 19%), and partial responses (6%). The median duration of ...

6. ashpublications.org ashpublications.org/blood/article/134/Supplement_1/3176/423805/Safety-and-Preliminary-Clinical-Activity-of

Safety and Preliminary Clinical Activity of REGN5458, an Anti ... Safety and Preliminary Clinical Activity of REGN5458, an Anti-Bcma x Anti-CD3 Bispecific Antibody, in Patients with Relapsed/Refractory Multiple ...

7. onclive.com onclive.com/view/dr-lee-on-the-updated-efficacy-and-safety-data-for-linvoseltamab-in-r-r-multiple-myeloma

Dr Lee on the Updated Efficacy and Safety Data ... Regarding safety, linvoseltamab had a generally manageable toxicity profile with no new safety signals at the time of follow-up, Lee states.