Linvoseltamab for Multiple Myeloma

(IMMUNOPLANT Trial)

Overseen By Dickran Kazandjian, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Dickran Kazandjian, MD

Must not be taking: Corticosteroids, Investigational agents, Live vaccines

Disqualifiers: HIV, Hepatitis B, Hepatitis C, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: 16-24 weeks

28 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if Linvoseltamab (also known as REGN-5458, a BCMAxCD3 antibody from Regeneron Pharmaceuticals) can control multiple myeloma, a type of blood cancer, by reducing residual cancer cells after initial treatment. It also examines the treatment's benefits and side effects. Prospective participants have been newly diagnosed with multiple myeloma, have already tried a specific combination therapy, and still show signs of the disease. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take certain medications like high-dose corticosteroids or other investigational agents. It's best to discuss your specific medications with the study team.

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

Research has shown that Linvoseltamab has promising safety results from earlier studies. Researchers tested it on patients with relapsed or refractory multiple myeloma, where the disease did not improve with previous treatments or returned after treatment. The results demonstrated that Linvoseltamab led to strong and lasting improvements, indicating its effectiveness over time. Importantly, patients generally tolerated it well, and it was safe.

While some side effects may occur, as with many treatments, data suggest that Linvoseltamab is generally safe to manage. This should reassure those considering joining a trial, but discussing any concerns with a doctor is always advisable. ^{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 proteasome inhibitors and immunomodulatory drugs, Linvoseltamab stands out due to its targeted action as a bispecific antibody. This drug works by specifically binding to both the cancer cells and immune cells, directing the body's immune system to attack and eliminate the cancer cells more effectively. Researchers are excited about Linvoseltamab because it offers a potentially more precise attack on cancer, which might translate to better outcomes with fewer side effects compared to traditional chemotherapy. Additionally, its unique mechanism could provide a new line of therapy for patients who have not responded well to existing treatments.

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

Research shows that Linvoseltamab, the investigational treatment in this trial, holds strong potential for treating multiple myeloma. In patients whose multiple myeloma returned or did not respond to other treatments, Linvoseltamab led to significant and lasting improvements. On average, these improvements lasted about 29.4 months, indicating long-term benefits for many patients. This drug targets a protein called BCMA on myeloma cells, aiding the immune system in attacking them. These early findings suggest that Linvoseltamab could effectively manage multiple myeloma by reducing disease activity and maintaining control over time. ^{1 2 6 7 8}

Who Is on the Research Team?

Dickran Kazandjian, MD

Principal Investigator

University of Miami

Are You a Good Fit for This Trial?

This trial is for individuals who have just been diagnosed with multiple myeloma, a type of blood cancer. Participants should not have received prior treatment for their condition and must be positive for minimal residual disease (MRD), which means there are still cancer cells after initial therapy.

Inclusion Criteria

I've had a treatment combo with at least two drugs from specified groups for my condition.

I can perform all my self-care but cannot work, or I am fully active. My ECOG is 1 or less, or it's 2 only because of myeloma pain.

My cancer responded well to treatment but still shows minimal signs.

Exclusion Criteria

Patients with HIV-positive status or hepatitis B or C infection

Any condition that, in the opinion of the Investigator, would compromise the well-being of the patient or the study or prevent the patient from meeting or performing study requirements

I am capable of making my own health decisions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Linvoseltamab for four to six 28-day cycles, depending on MRD conversion status

16-24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 2 years

Extension

Participants may continue to be monitored for overall survival and progression-free survival

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Linvoseltamab

Trial Overview The study is testing Linvoseltamab, a new potential therapy for multiple myeloma. The goal is to see if this treatment can eliminate the remaining cancer cells to achieve MRD-negative status and help control the disease longer than current treatments.

How Is the Trial Designed?

Group I: Linvoseltamab Group Experimental Treatment 1 Intervention

Participants in this group will be administered a fixed duration of Linvoseltamab for four to six 28-day cycles, depending on minimal residual disease (MRD) conversion status. After four cycles, participants that are MRD-negative will no longer receive study treatment. Participants that are MRD-positive will receive an additional two cycles of Linvoseltamab. Total participation duration is up to 3 years.

Who Is Running the Clinical Trial?

Dickran Kazandjian, MD

Lead Sponsor

Trials

1

Recruited

30+

Regeneron Pharmaceuticals

Industry 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

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]

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]

Anti-B-cell maturation antigen (BCMA) therapies, including bispecific antibodies and CAR T cells, have shown effectiveness in treating relapsed refractory multiple myeloma, with all four reviewed agents receiving FDA approval for adult patients.

However, these therapies can lead to severe side effects such as cytokine release syndrome and neurotoxicity, which can be life-threatening; the review emphasizes the importance of understanding these complications and outlines management strategies to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Adverse Reactions for BCMA-Directed Therapy in Relapsed Multiple Myeloma: A Focused Review. Khanam, R., Faiman, B., Batool, S., et al.[2023]

Monoclonal antibodies, such as daratumumab and isatuximab, have significantly improved treatment outcomes for multiple myeloma patients, being effective from first-line therapy to cases of refractory disease.

Belantamab mafodotin, the first antibody drug conjugate targeting B cell maturation antigen, is now approved for use as a monotherapy in advanced multiple myeloma, showcasing the potential of novel agents in enhancing patient prognosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal Antibodies and Antibody Drug Conjugates in Multiple Myeloma. Radocha, J., van de Donk, NWCJ., Weisel, K.[2023]

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]

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]

In a study of 14 patients with newly diagnosed multiple myeloma, the combination of siltuximab with lenalidomide, bortezomib, and dexamethasone showed a high overall response rate of 90.9%, indicating strong efficacy in treating this condition.

The maximum tolerated dose of siltuximab was determined to be 8.3 mg/kg, with serious adverse events including grade 3 pneumonia and grade 4 thrombocytopenia, but no deaths occurred during the study, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Siltuximab (CNTO 328) with lenalidomide, bortezomib and dexamethasone in newly-diagnosed, previously untreated multiple myeloma: an open-label phase I trial. Shah, JJ., Feng, L., Thomas, SK., et al.[2018]

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]

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]

In a real-world study involving four patients with relapsed/refractory multiple myeloma (RRMM), isatuximab-based therapy showed clinical benefits, even in patients previously treated with daratumumab, indicating that prior anti-CD38 therapy does not prevent a positive response to isatuximab.

The findings also suggest that isatuximab can be safely used in patients with renal insufficiency, further supporting its potential as a treatment option for diverse patient profiles in RRMM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world experience with isatuximab in the treatment of relapsed-refractory multiple myeloma: a case series from the Grand Duchy of Luxembourg. De Wilde, S., Plawny, L., Berchem, G.[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]

Isatuximab, an anti-CD38 monoclonal antibody, was found to be well tolerated and effective in treating heavily pretreated relapsed/refractory multiple myeloma, with an overall response rate of 36.4% in a phase 2 trial involving 28 patients.

The most common side effects were mild infusion reactions occurring in 42.9% of patients, indicating a manageable safety profile, while the median progression-free survival was 4.7 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isatuximab monotherapy in relapsed/refractory multiple myeloma: A Japanese, multicenter, phase 1/2, safety and efficacy study. Sunami, K., Suzuki, K., Ri, M., et al.[2020]

Ciltacabtagene autoleucel (cilta-cel) demonstrated significantly improved efficacy compared to three non-CAR-T therapies for treating relapsed or refractory multiple myeloma, with at least a 3.1-fold increase in overall response rates and a 10.3-fold increase in complete response rates.

Patients receiving cilta-cel experienced at least a 74% reduction in the risk of disease progression or death and a 47% reduction in the risk of death, indicating its strong potential as a treatment option for patients who have been previously treated with multiple therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-Adjusted Indirect Treatment Comparison to Assess the Comparative Efficacy of Ciltacabtagene Autoleucel in CARTITUDE-1 Versus Belantamab Mafodotin in DREAMM-2, Selinexor-Dexamethasone in STORM Part 2, and Melphalan Flufenamide-Dexamethasone in HORIZON for the Treatment of Patients With Triple-Class Exposed Relapsed or Refractory Multiple Myeloma. Weisel, K., Krishnan, A., Schecter, JM., 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. 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.

3. 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.

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 ... “This approval provides a highly effective, off-the-shelf agent for the treatment of [patients with] relapsed/refractory multiple myeloma,” Lee ...

6. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/7056/527036/Exposure-Response-Analyses-of-Various-Efficacy-and

Exposure-Response Analyses of Various Efficacy and Safety ... Linvoseltamab, an investigational BCMAxCD3 bispecific antibody, for the treatment of patients with relapsed or refractory multiple myeloma.

7. 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 ... Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy. ... REGN5458 in a first-in-human trial ...

8. ajmc.com ajmc.com/view/linvoseltamab-shows-durable-efficacy-manageable-safety-in-r-r-multiple-myeloma

Linvoseltamab Shows Durable Efficacy, Manageable ... Linvoseltamab is a BCMA [B-cell maturation antigen] and CD3 bispecific antibody that was studied in patients with relapsed, refractory multiple myeloma.