Elranatamab Combinations for Multiple Myeloma

(MAGNETISMM-5 Trial)

Recruiting at 315 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Pfizer

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

759 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate whether the BCMA-CD3 bispecific antibody elranatamab, alone and/or in combination with the anti-CD38 monoclonal antibody, daratumumab, can provide more benefit to people with multiple myeloma compared to a combination therapy including daratumumab, pomalidomide, and dexamethasone. People with multiple myeloma who have received previous treatment including lenalidomide and a proteasome inhibitor will be enrolled in the study. Part 1 of the study will assess the safety and activity of different doses of elranatamab in combination with daratumumab. People participating in Part 2 of the study will be randomly assigned to receive either elranatamab alone, elranatamab plus daratumumab, or daratumumab, pomalidomide, and dexamethasone. Part 2 will compare the safety and activity of (1) elranatamab alone compared to daratumumab, pomalidomide, and dexamethasone, and (2) elranatamab plus daratumumab compared to daratumumab, pomalidomide, and dexamethasone. Participants in all parts of the study will receive study treatment until their disease progresses, they experience unacceptable side effects, or they choose to no longer participate in the study.

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

The trial protocol does not specify if you need to stop your current medications. However, you cannot have had anti-CD38 therapy within 6 months before the trial or any investigational product within 30 days before the trial.

What data supports the idea that Elranatamab Combinations for Multiple Myeloma is an effective drug?

The available research shows that Daratumumab, a part of the Elranatamab Combinations for Multiple Myeloma, is effective in treating multiple myeloma. Studies have shown that when used alone or with other drugs like lenalidomide and dexamethasone, it helps patients who have relapsed or have not responded to other treatments. In one study, about 30% of patients responded positively to Daratumumab alone. When combined with other drugs, it significantly increased the time patients lived without the disease getting worse. It also improved some aspects of patients' quality of life. Compared to other treatments, Daratumumab has shown deep and lasting responses, making it a valuable option for patients with multiple myeloma. ^{1 2 3 4 5}

What safety data is available for Elranatamab combinations in treating multiple myeloma?

The safety data for Elranatamab combinations in treating multiple myeloma can be inferred from studies on Daratumumab, a monoclonal antibody targeting CD38, which is often used in combination with other agents like dexamethasone and pomalidomide. Daratumumab has shown a favorable toxicity profile with common adverse events being hematological, such as neutropenia and lymphopenia. Infusion-related reactions are also noted, but overall, it has an acceptable safety profile both as a monotherapy and in combination therapies. The safety data for Elranatamab specifically may not be directly available, but similar monoclonal antibodies like Daratumumab provide a basis for understanding potential safety considerations. ^{3 4 6 7 8}

Is the drug Daratumumab, Elranatamab a promising treatment for multiple myeloma?

Yes, Daratumumab, Elranatamab is a promising treatment for multiple myeloma. Elranatamab has shown strong results in clinical trials, with a high response rate and long-lasting effects in patients who have tried other treatments. It has been approved in the USA and is being reviewed in other countries. Daratumumab has also been effective, especially when combined with other drugs, providing deep and lasting responses. ^{1 2 9 10 11}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for adults with multiple myeloma who've had prior treatments including lenalidomide and a proteasome inhibitor. They should have measurable disease, be in relatively good health (ECOG ≤2), not pregnant, and willing to use contraception. Excluded are those with certain other conditions like amyloidosis or active infections, previous BCMA therapy, recent stem cell transplant, or live vaccines taken within the last month.

Inclusion Criteria

I have been diagnosed with multiple myeloma.

You have certain levels of abnormal proteins in your blood or urine, or abnormal levels of certain proteins in your blood.

I have been treated for multiple myeloma with lenalidomide and a proteasome inhibitor.

Exclusion Criteria

I have been treated with a BCMA-targeted therapy before.

I have been diagnosed with amyloidosis.

I do not have any active infections like HBV, HCV, HIV, or uncontrolled bacterial, fungal, or viral infections.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part 1: Safety Lead-In Dose Escalation

Assessment of safety and activity of different doses of elranatamab in combination with daratumumab

8-12 weeks

Part 2: Randomized Treatment

Participants receive either elranatamab alone, elranatamab plus daratumumab, or daratumumab, pomalidomide, and dexamethasone until disease progression or unacceptable side effects

Until disease progression

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Daratumumab
• Dexamethasone
• Elranatamab
• Pomalidomide

Trial Overview The study tests elranatamab alone or combined with daratumumab against a known combo of daratumumab, pomalidomide & dexamethasone in relapsed/refractory multiple myeloma patients. It's divided into parts: assessing safety and activity of different doses; comparing these treatments; evaluating alternative dosing schedules.

Participant Groups

Group I: Part 2 Randomized Arm B: Elranatamab + Daratumumab Experimental Treatment 2 Interventions

Group II: Part 2 Randomized Arm A: Elranatamab Experimental Treatment 1 Intervention

Group III: Part 1 Safety Lead-In Dose Escalation: Elranatamab + Daratumumab Experimental Treatment 2 Interventions

Group IV: Part 2 Randomized Arm C: Daratumumab + Pomalidomide + Dexamethasone Active Control 3 Interventions

Daratumumab is already approved in European Union, United States for the following indications:

Approved in European Union as Darzalex for:

• Relapsed and refractory multiple myeloma
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone

Approved in United States as Darzalex for:

• Multiple myeloma in patients who have received at least three prior therapies
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone
• Relapsed or refractory multiple myeloma in combination with lenalidomide and dexamethasone

Who Is Running the Clinical Trial?

Pfizer

Lead Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

Findings from Research

Daratumumab, a monoclonal antibody targeting CD38, has shown significant efficacy as a monotherapy in relapsed/refractory multiple myeloma, achieving an overall response in about one-third of patients, with rapid and durable effects.

In combination with other treatments like bortezomib or lenalidomide, daratumumab significantly prolonged progression-free survival, although the overall survival benefit is still being evaluated, and it was generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Relapsed and/or Refractory Multiple Myeloma. Blair, HA.[2018]

Daratumumab, a monoclonal antibody targeting CD38, has been approved in the USA for treating multiple myeloma in patients who have undergone at least three prior therapies, demonstrating its role as a treatment option for difficult-to-treat cases.

In a phase II trial, daratumumab monotherapy showed an overall response rate of about 30% in patients with relapsed or refractory multiple myeloma, indicating its efficacy in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: First Global Approval. McKeage, K.[2018]

Daratumumab is a monoclonal antibody that effectively targets CD38 on multiple myeloma cells, leading to cell death through various mechanisms such as complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity.

It has shown a favorable safety profile and significant clinical activity as both a standalone treatment and in combination with lenalidomide for patients with relapsed multiple myeloma who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. Xia, C., Ribeiro, M., Scott, S., et al.[2018]

Intravenous daratumumab, when combined with bortezomib, thalidomide, and dexamethasone, significantly improves treatment outcomes for adults with newly diagnosed multiple myeloma, leading to higher rates of stringent complete response and prolonged progression-free survival, as shown in the phase III CASSIOPEIA trial.

The addition of daratumumab has a minimal impact on overall toxicity, with the most common serious side effects being blood-related issues, indicating it is a relatively safe option for patients undergoing treatment for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma. Lamb, YN.[2021]

In a phase 3 trial with 569 patients, the addition of daratumumab to lenalidomide and dexamethasone significantly improved progression-free survival, with only 18.5% of patients experiencing disease progression compared to 41.0% in the control group.

Daratumumab also resulted in a higher overall response rate (92.9% vs. 76.4%) and a greater percentage of patients achieving minimal residual disease status (22.4% vs. 4.6%), although it was associated with a higher incidence of neutropenia and infusion-related reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. Dimopoulos, MA., Oriol, A., Nahi, H., et al.[2022]

Daratumumab has shown single-agent effectiveness in treating refractory multiple myeloma, while both daratumumab and elotuzumab demonstrate significant activity when used in combination with other treatments like proteasome inhibitors and immunomodulatory agents.

The incorporation of these monoclonal antibodies into treatment regimens is expected to greatly enhance outcomes for multiple myeloma patients, with ongoing trials focusing on the best timing and duration for their use in various treatment phases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How to Integrate Elotuzumab and Daratumumab Into Therapy for Multiple Myeloma. Hofmeister, CC., Lonial, S.[2018]

Daratumumab, an anti-CD38 monoclonal antibody, has significantly improved treatment outcomes for multiple myeloma (MM), showing enhanced progression-free survival and response rates in relapsed/refractory cases when combined with other therapies, as demonstrated in several key clinical trials.

In newly diagnosed patients, daratumumab has also shown an overall survival benefit when added to frontline treatment regimens, indicating its effectiveness in both early and advanced stages of MM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab for the Treatment of Multiple Myeloma: A Review of Clinical Applicability and Operational Considerations. Arnall, JR., Maples, KT., Harvey, RD., et al.[2022]

Elotuzumab and daratumumab are two monoclonal antibodies approved for treating relapsed or refractory multiple myeloma, with both enhancing immune system activity against myeloma cells; elotuzumab is used with lenalidomide and dexamethasone for better outcomes, while daratumumab can be effective alone or with other treatments.

The main side effects of these treatments are allergic-type infusion reactions, and there are important considerations regarding their impact on laboratory tests and potential cross-reactivity with red blood cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monoclonal Antibodies in Multiple Myeloma: A New Wave of the Future. Sherbenou, DW., Mark, TM., Forsberg, P.[2018]

In the MagnetisMM-1 trial involving 88 patients with relapsed or refractory multiple myeloma, elranatamab demonstrated a significant overall response rate of 63.6%, with 38.2% of patients achieving a complete response or better, indicating its efficacy even in heavily pre-treated patients.

Elranatamab showed manageable safety with no dose-limiting toxicities during dose escalation, although some patients experienced cytopenias and cytokine release syndrome; the median progression-free survival was 11.8 months and overall survival was 21.2 months, suggesting promising durability of responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elranatamab in relapsed or refractory multiple myeloma: the MagnetisMM-1 phase 1 trial. Bahlis, NJ., Costello, CL., Raje, NS., et al.[2023]

Elranatamab is a bispecific T cell engager that targets BCMA on multiple myeloma cells, effectively activating T cells to kill these cancer cells, and has received its first approval in the USA for treating adult patients with relapsed or refractory multiple myeloma after at least four prior therapies.

The approval was based on the drug's response rate and durability of response, with ongoing studies required to confirm its clinical benefits, indicating a promising new option for patients with difficult-to-treat multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elranatamab: First Approval. Dhillon, S.[2023]

Elranatamab, a bispecific antibody targeting BCMA and CD3, has shown promising results in treating relapsed refractory multiple myeloma, but its effectiveness in cases with central nervous system (CNS) involvement was previously unclear.

In a reported case, a 37-year-old male patient with CNS involvement of multiple myeloma was successfully treated with Elranatamab, suggesting potential for this therapy in challenging CNS-MM cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Relapsed refractory multiple myeloma with CNS involvement successfully treated with Elranatamab: first reported case. Mutlu, YG., Yıgıt Kaya, S., Maral, S., et al.[2023]

References

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

Daratumumab: A Review in Relapsed and/or Refractory Multiple Myeloma. [2018]

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

Daratumumab: First Global Approval. [2018]

3. Spain pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. [2018]

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

Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma. [2021]

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

Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. [2022]

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

How to Integrate Elotuzumab and Daratumumab Into Therapy for Multiple Myeloma. [2018]

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

Daratumumab for the Treatment of Multiple Myeloma: A Review of Clinical Applicability and Operational Considerations. [2022]

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

Monoclonal Antibodies in Multiple Myeloma: A New Wave of the Future. [2018]

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

Elranatamab in relapsed or refractory multiple myeloma: the MagnetisMM-1 phase 1 trial. [2023]

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

Elranatamab: First Approval. [2023]

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

Relapsed refractory multiple myeloma with CNS involvement successfully treated with Elranatamab: first reported case. [2023]