Linvoseltamab Combo for Multiple Myeloma

Recruiting at 54 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

Trial Summary

What is the purpose of this trial?

This study is researching an experimental drug called linvoseltamab in combination with other drugs for the treatment of a blood cancer called multiple myeloma. Linvoseltamab has previously been studied as a single agent (without other cancer treatments) in participants with multiple myeloma that returned after prior therapies and needed to be treated again. In the initial study, some participants treated with linvoseltamab had improvement of their myeloma, including complete responses (no evidence of myeloma in their bodies). This study is the first time linvoseltamab will be combined with other cancer therapies. The main goal is to understand if linvoseltamab can be given safely with other cancer treatments, and if so, what dose of linvoseltamab should be used for each combination. The study is looking at several other research questions, including: * How many participants treated with linvoseltamab in combination with each of the other cancer treatments have improvement of their multiple myeloma * What side effects may happen from taking linvoseltamab together with another cancer treatment * How much study drug is in the blood at different times * Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects)

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.

What data supports the effectiveness of the drug Linvoseltamab Combo for Multiple Myeloma?

Monoclonal antibodies, like those in Linvoseltamab Combo, have shown promise in treating multiple myeloma by targeting specific proteins on cancer cells, leading to their destruction. Similar treatments, such as those targeting BCMA, have demonstrated encouraging results in clinical trials, suggesting potential effectiveness for Linvoseltamab Combo. ^{1 2 3 4 5}

What is known about the safety of Linvoseltamab Combo for Multiple Myeloma?

Linvoseltamab, also known as REGN5458, is a bispecific antibody targeting BCMA and CD3, similar to other treatments like teclistamab. These treatments can cause side effects such as cytokine release syndrome (a condition where the immune system releases too many proteins into the blood too quickly) and neurotoxicity (damage to the nervous system), with incidence rates ranging from 40% to 90% for cytokine release syndrome and 3% to 20% for neurotoxicity. ^{5 6 7 8 9}

What makes the drug Linvoseltamab unique for treating multiple myeloma?

Linvoseltamab is unique because it is a bispecific antibody that targets both BCMA (B-cell maturation antigen) on myeloma cells and CD3 on T-cells, helping the immune system directly attack the cancer cells. This dual-targeting approach is different from other treatments that typically focus on a single target. ^{1 2 5 10 11}

Research Team

Clinical Trial Management

Principal Investigator

Regeneron Pharmaceuticals

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

Group I: Cohort 9: Linvoseltamab + Nirogacestat Experimental Treatment 1 Intervention

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

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

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Elotuzumab Therapy for Relapsed or Refractory Multiple Myeloma. [2022]

2. England pubmed.ncbi.nlm.nih.gov

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

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

Current antibody-based therapies for the treatment of multiple myeloma. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Therapeutic Monoclonal Antibodies and Antibody Products: Current Practices and Development in Multiple Myeloma. [2020]

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

Isatuximab in combination with cemiplimab in patients with relapsed/refractory multiple myeloma: A phase 1/2 study. [2023]

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

T cell redirecting bispecific antibodies for multiple myeloma: emerging therapeutic strategies in a changing treatment landscape. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Monoclonal antibodies as an addition to current myeloma therapy strategies. [2021]

8. New Zealand pubmed.ncbi.nlm.nih.gov

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

9. Switzerland pubmed.ncbi.nlm.nih.gov

Ciltacabtagene autoleucel: The second anti-BCMA CAR T-cell therapeutic armamentarium of relapsed or refractory multiple myeloma. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Therapeutic antibodies for multiple myeloma. [2018]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Investigational Monoclonal Antibodies in the Treatment of Multiple Myeloma: A Systematic Review of Agents under Clinical Development. [2023]