Linvoseltamab Combo for Multiple Myeloma

Recruiting at 77 trial locations

Overseen By Clinical Trials Administrator

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Regeneron Pharmaceuticals

Must not be taking: BCMA immunotherapies, Anti-PD-1, others

Disqualifiers: Plasma cell leukemia, Brain lesions, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 28 days

317 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug called linvoseltamab (also known as REGN5458, a BCMAxCD3 antibody) to determine if it can be safely combined with other treatments for multiple myeloma, a type of blood cancer. Researchers aim to find the best dose and assess whether this combination improves the condition by reducing or eliminating the cancer. They will also monitor for any side effects and observe how the body reacts to the drug. Individuals with multiple myeloma that has returned or worsened after at least three other treatments might be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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

The trial requires a 6-month period without certain prior treatments like anti-CD38 antibodies, carfilzomib, lenalidomide, bortezomib, and pomalidomide before joining. If you are on these medications, you will need to stop them for this period before participating.

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

Research has shown that linvoseltamab, when used alone, generally has a manageable safety profile for individuals with relapsed or refractory multiple myeloma. Some studies have reported a high rate of positive responses, with these responses being deep and lasting.

When combined with carfilzomib, the safety remains consistent with known profiles of each drug. Some side effects are expected but considered manageable.

In combinations with bortezomib, the safety profile is also similar to what is known for each drug, with a comparable risk of severe infection as seen with linvoseltamab alone.

For the combination with daratumumab, linvoseltamab has demonstrated an acceptable safety profile, leading to deep and lasting responses in patients.

Each combination aims to maintain the manageable safety observed with linvoseltamab alone. However, since this trial is in an early phase, it primarily focuses on understanding how these combinations work and what side effects might occur. More safety data will be collected as research continues. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about linvoseltamab combinations for multiple myeloma because this approach targets the disease in novel ways. Unlike many current treatments that focus on standard chemotherapy or proteasome inhibition, linvoseltamab is an antibody-based therapy that works by harnessing the immune system to directly target and kill cancer cells. It is combined with various other drugs like cevostamab and daratumumab, each offering unique mechanisms to enhance the treatment's effectiveness. This innovative strategy could lead to more personalized and potentially more effective treatment options for patients with multiple myeloma.

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

Research has shown that linvoseltamab may effectively treat multiple myeloma, a type of blood cancer. In earlier studies, linvoseltamab led to significant and lasting improvements in patients, with some experiencing complete responses, meaning no signs of cancer were found. This trial tests linvoseltamab in combination with various other drugs, such as carfilzomib and bortezomib, in different treatment arms. These combinations have shown a high rate of strong responses in previous studies, suggesting they could be very effective. Linvoseltamab targets a specific protein on cancer cells, potentially helping the immune system attack the cancer more effectively. Overall, early findings suggest that linvoseltamab, when combined with other treatments, could improve outcomes for patients with multiple myeloma. ^{2 5 6 7 8}

Who Is on the Research Team?

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Are You a Good Fit for This Trial?

Adults with multiple myeloma resistant to standard treatments can join this trial. They must have tried at least three therapies, or two if they've had specific drugs. Good kidney, blood, and liver function are needed, along with a life expectancy of over six months. Certain prior treatments require a waiting period before joining.

Inclusion Criteria

I have RRMM, tried 3 treatments including anti-CD38, IMiD, and PI, or my disease resisted these treatments.

I have taken bortezomib before and tolerated it well, or I am resistant to multiple myeloma treatments but haven't taken bortezomib in the last 6 months.

I have had isatuximab before and tolerated it well. It's been 3 months since my last anti-CD38 therapy.

Exclusion Criteria

I have not received a live vaccine within the last 28 days.

I do not have conditions that affect how my body absorbs medication.

I have been diagnosed with a specific blood or bone marrow condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive linvoseltamab in combination with other cancer treatments to determine safety and optimal dosing

28 days

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Linvolseltamab

Trial Overview The trial tests linvoseltamab combined with other cancer drugs in patients whose multiple myeloma has returned after treatment. It aims to find the safe dose for combinations and see how well they work together against the cancer.

How Is the Trial Designed?

Group I: Cohort 9: Linvoseltamab + Nirogacestat Experimental Treatment 2 Interventions

Linvoseltamab + Nirogacestat

Group II: Cohort 8: Linvoseltamab + Cemiplimab Experimental Treatment 2 Interventions

Linvoseltamab + Cemiplimab

Group III: Cohort 7: Linvoseltamab + Fianlimab Experimental Treatment 2 Interventions

Linvoseltamab + Fianlimab

Group IV: Cohort 6: Linvoseltamab + Isatuximab Experimental Treatment 2 Interventions

Linvoseltamab + Isatuximab

Group V: Cohort 5: Linvoseltamab + Pomalidomide Experimental Treatment 2 Interventions

Linvoseltamab + Pomalidomide

Group VI: Cohort 4: Linvoseltamab + Bortezomib Experimental Treatment 2 Interventions

Linvoseltamab + Bortezomib

Group VII: Cohort 3: Linvoseltamab + Lenalidomide Experimental Treatment 2 Interventions

Linvoseltamab + Lenalidomide

Group VIII: Cohort 2: Linvolseltamab + Carfilzomib Experimental Treatment 2 Interventions

Linvoseltamab + Carfilzomib

Group IX: Cohort 1: Linvoseltamab + Daratumumab Experimental Treatment 2 Interventions

Linvoseltamab + Daratumumab

Group X: Cohort 10: Linvoseltamab + Cevostamab Experimental Treatment 2 Interventions

Linvoseltamab + Cevostamab

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 is the first bispecific antibody approved for treating relapsed or refractory multiple myeloma, showing impressive efficacy in heavily pretreated patients, making it a promising option in this challenging area of treatment.

While teclistamab offers significant benefits, it also has notable adverse effects such as cytokine release syndrome, infections, and neurotoxicity, requiring careful management and precautions by healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teclistamab for Multiple Myeloma: Clinical Insights and Practical Considerations for a First-in-Class Bispecific Antibody. Pan, D., Richter, J.[2023]

Monoclonal antibodies, such as daratumumab and isatuximab targeting CD38, and elotuzumab targeting SLAMF7, are emerging as effective salvage therapies for patients with relapsed or refractory multiple myeloma, based on recent literature up to March 2020.

These therapies are expected to significantly change treatment strategies for myeloma, but careful consideration of their combinations and potential new toxicities will be crucial for future patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibodies in relapsed/refractory myeloma: updated evidence from clinical trials, real-life studies, and meta-analyses. Musto, P., La Rocca, F.[2021]

Anti-CD38 monoclonal antibodies have become a standard treatment for multiple myeloma, significantly enhancing patient response when used alongside traditional therapies.

New therapies targeting BCMA, including drug conjugates and bispecific T-cell engagers, show promise as effective options for treating multiple myeloma, particularly in patients who have become resistant to existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal antibodies as an addition to current myeloma therapy strategies. Jullien, M., Touzeau, C., Moreau, P.[2021]

Monoclonal antibodies, such as daratumumab and elotuzumab, have significantly improved treatment outcomes for multiple myeloma (MM), particularly in patients who are double-refractory, and are becoming essential in the initial treatment of newly diagnosed MM.

The recent approval of belantamab mafodotin, which targets B-cell maturation antigen (BCMA), marks a significant advancement in antibody therapies for advanced MM, demonstrating promising efficacy and manageable toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current antibody-based therapies for the treatment of multiple myeloma. Varga, C., Waldschmidt, JM., Gandolfi, S., et al.[2021]

Monoclonal antibodies (mAbs) are a promising new treatment for multiple myeloma (MM), with two already approved: daratumumab for newly diagnosed and relapsed patients, and elotuzumab for relapsed cases.

mAbs work by targeting specific antigens on MM cells to induce cell death, enhance immune response, or deliver cytotoxic drugs, and ongoing clinical trials are exploring their effectiveness in combination with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Monoclonal Antibodies and Antibody Products: Current Practices and Development in Multiple Myeloma. Bonello, F., Mina, R., Boccadoro, M., 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]

Isatuximab (anti-CD38) and F50067 (anti-CXCR4) showed promising results as monotherapies in treating multiple myeloma, with overall response rates of 66.7% and 32%, respectively, based on a review of 39 studies involving 1906 patients.

Combination therapies using Isatuximab with lenalidomide and dexamethasone achieved a clinical benefit rate of 83%, while Indatuximab Ravtansine showed response rates of 78% and 79% when combined with these agents, indicating that mAbs can enhance treatment efficacy when used alongside traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigational Monoclonal Antibodies in the Treatment of Multiple Myeloma: A Systematic Review of Agents under Clinical Development. Iftikhar, A., Hassan, H., Iftikhar, N., et al.[2023]

In a phase 3 study involving 646 patients with relapsed or refractory multiple myeloma, the combination of elotuzumab, lenalidomide, and dexamethasone significantly improved progression-free survival, with a median of 19.4 months compared to 14.9 months for the control group.

The overall response rate was also higher in the elotuzumab group at 79% versus 66% in the control group, indicating that elotuzumab enhances the effectiveness of standard treatment for this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma. Lonial, S., Dimopoulos, M., Palumbo, A., et al.[2022]

In a Phase 1/2 trial involving 106 patients with relapsed and refractory multiple myeloma, the combination of cemiplimab (anti-PD-1) and isatuximab (anti-CD38) showed a marginal increase in response rates, with 25% of patients responding in the cemiplimab combination groups compared to 11.8% in the isatuximab-only group.

Despite the increased response rates, the addition of cemiplimab did not lead to statistically significant improvements in progression-free or overall survival after a median follow-up of nearly 10 months, and there were no major safety concerns associated with the combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab in combination with cemiplimab in patients with relapsed/refractory multiple myeloma: A phase 1/2 study. Lesokhin, A., LeBlanc, R., Dimopoulos, MA., et al.[2023]

Elotuzumab, an antibody targeting SLAMF7, has been shown to reduce the risk of disease progression or death by 30% when combined with lenalidomide and dexamethasone in patients with relapse/refractory multiple myeloma, based on the ELOQUENT-2 trial.

Daratumumab, targeting CD38, demonstrated significantly improved complete response rates and progression-free survival in multiple myeloma patients when combined with bortezomib and dexamethasone, as well as with lenalidomide and dexamethasone, in the CASTOR and POLLUX trials, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic antibodies for multiple myeloma. Ishida, T.[2018]

Ciltacabtagene autoleucel (cilta-cel) is a CAR T-cell therapy that effectively targets B-cell maturation antigen (BCMA) in patients with relapsed or refractory multiple myeloma, showing early and long-lasting responses based on the Phase 1b/2 CARTITUDE-1 study.

While cilta-cel has a tolerable safety profile with manageable adverse effects, it generally demonstrates better efficacy compared to another CAR T-cell therapy, idecabtagene vicleucel (ide-cel), although both therapies have comparable adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ciltacabtagene autoleucel: The second anti-BCMA CAR T-cell therapeutic armamentarium of relapsed or refractory multiple myeloma. Chekol Abebe, E., Yibeltal Shiferaw, M., Tadele Admasu, F., et al.[2022]

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7510

Linvoseltamab (LINVO) + bortezomib (BTZ) in patients (pts) ... Background: LINVO, a BCMA×CD3 bispecific antibody, has shown high efficacy and generally manageable safety in triple-class exposed (TCE: anti- ...

2. newsroom.regeneron.com newsroom.regeneron.com/news-releases/news-release-details/linvoseltamab-combination-carfilzomib-or-bortezomib-shows

Linvoseltamab in Combination with Carfilzomib or ... Linvoseltamab in Combination with Carfilzomib or Bortezomib Shows Promising Initial Results in Earlier Lines of Treatment for Relapsed/Refractory Multiple ...

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

Comparative Effectiveness of Linvoseltamab Versus Current ... The aim of this study was to compare ORR, overall and in key subgroups, between patients in Phase 2 of the LINKER-MM1 trial and patients in an ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT05137054

NCT05137054 | A Study to Examine the Effects of Novel ... In the initial study, some participants treated with linvoseltamab had improvement of their myeloma, including complete responses (no evidence of myeloma in ...

5. springworkstx.com springworkstx.com/wp-content/uploads/2023/08/Rodriguez-Otero_REGN5458-TiP-Ph-1b-Multi-Cohort-Study-of-Combination-Regimens-for-RRMM_ASH22.pdf

Linvoseltamab (REGN5458), a BCMAXCD3 Bispecific ... BCMA is a cell surface protein expressed on malignant plasma cells³. Notably, BCMA is detected only at low levels on normal plasma cells, activated. B cells, ...

6. regeneronpharmaceuticalsinc.gcs-web.com regeneronpharmaceuticalsinc.gcs-web.com/static-files/67055c32-348a-4851-b6e6-b03c535af879

Safety and Preliminary Clinical Activity of REGN5458, an Anti ... Summary. • A total of seven patients (median age 78 years) with R/R MM. (median seven lines of prior systemic therapies, all of whom failed.

7. targetedonc.com targetedonc.com/view/linvoseltamab-bortezomib-shows-consistent-safety-in-relapsed-refractory-multiple-myeloma

Linvoseltamab/Bortezomib Shows Consistent Safety in ... Linvoseltamab plus bortezomib showed a manageable safety profile and 85% ORR in relapsed/refractory multiple myeloma, with few discontinuations.

8. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/4444/492326/Trial-in-Progress-REGN5458-a-BCMAxCD3-Bispecific

REGN5458, a BCMAxCD3 Bispecific Antibody, in a Phase Ib ... A global, Phase Ib, open-label, multi-cohort study exploring REGN5458 in combination with other cancer treatments in patients with relapsed/refractory multiple ...