Elranatamab Combinations for Multiple Myeloma

(MAGNETISMM-5 Trial)

Recruiting at 356 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Pfizer

Must not be taking: BCMA-directed, Anti-CD38

Disqualifiers: Smoldering myeloma, Plasma cell leukemia, Amyloidosis, 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

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

Compensation: Varies

Number of Visits: Unknown

944 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the effectiveness of the new drug elranatamab, a potential treatment for multiple myeloma, a type of blood cancer. Researchers will test elranatamab alone and in combination with another drug, daratumumab, to determine if it surpasses the current standard treatment, which includes daratumumab, pomalidomide, and dexamethasone. The study will also evaluate whether additional protective measures can prevent infections during treatment. It targets individuals who have had multiple myeloma for some time and have already tried lenalidomide, a common treatment for this condition. 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.

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.

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

Research has shown that elranatamab is generally safe for people with multiple myeloma, a type of blood cancer. In studies, participants taking elranatamab alone experienced some side effects, but these were often manageable. Common issues included fatigue and low blood cell counts, which can increase tiredness and the risk of infections. Importantly, the FDA has already approved this treatment for patients who have tried several other therapies.

When combined with daratumumab, another cancer-fighting drug, elranatamab has demonstrated promising safety results. Research has not identified any new serious side effects with this combination. The combination is considered safe and manageable, with most side effects addressed through existing treatments or adjustments.

Overall, evidence suggests that elranatamab, whether used alone or with daratumumab, is relatively well-tolerated by patients. However, like any medication, it may cause side effects, and participants should discuss potential risks with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Elranatamab and its combinations for treating multiple myeloma because it offers a novel approach compared to traditional options like proteasome inhibitors and immunomodulatory drugs. Elranatamab is a bispecific antibody that targets both BCMA on myeloma cells and CD3 on T-cells, enhancing the immune system's ability to attack cancer cells directly. When combined with Daratumumab, an anti-CD38 monoclonal antibody, this treatment could potentially offer a more powerful and targeted attack on the cancer, improving patient outcomes. This innovative mechanism of action is why researchers are hopeful about its potential to improve the standard of care for multiple myeloma patients.

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

Research has shown that elranatamab, one of the treatments studied in this trial, may effectively treat multiple myeloma, a type of blood cancer. In one study, 26% of patients achieved a complete response, with no cancer detected in their blood or urine after treatment. Another study found that 61% of patients had an overall response, indicating significant improvement for many. In this trial, some participants will receive elranatamab alone, while others will receive a combination of elranatamab and daratumumab. Early results suggest this combination might be particularly effective for patients who cannot undergo transplants. This combination has shown promising results in other studies, indicating its potential effectiveness. ^{6 7 8 9 10}

Who Is on the Research Team?

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Part 3 Arm E: Elranatamab + Daratumumab Experimental Treatment 2 Interventions

Group II: Part 3 Arm D: Elranatamab Experimental Treatment 1 Intervention

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

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

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

Group VI: 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

Published Research Related to This Trial

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]

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]

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, 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 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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40826257/

Population Exposure-Response Efficacy Analysis of ... Results from the MagnetisMM-3 study indicated deep and durable responses in patients with relapsed or refractory multiple myeloma (RRMM).

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7549

A US subgroup analysis from MagnetisMM-3. Background: The ongoing phase 2 MagnetisMM-3 (NCT04649359) study demonstrated the efficacy and safety of ELRA in patients (pts) with RRMM ...

3. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-025-14624-9

Comparison of outcomes with elranatamab and real world ... This study aimed to characterise outcomes for real world TCE RRMM patients and to estimate the treatment effect of elranatamab compared to ...

4. elrexfio.com elrexfio.com/results

ELREXFIO® (elranatamab-bcmm) Results | Safety Info In Group A, results with ELREXFIO showed: 26% of people had a CR or better: Multiple myeloma could not be detected in the blood or urine after treatment. 26% of ...

5. nature.com nature.com/articles/s41591-023-02528-9

Elranatamab in relapsed or refractory multiple myeloma Responses were consistent across BICR, investigator and a computerized algorithm, with an ORR of 61.0% (95% CI: 51.8–69.6), 59.3% (95% CI: 50.1– ...

6. elrexfio.com elrexfio.com/

ELREXFIO® (elranatamab-bcmm) Info for Patients | Safety Info Find information on FDA-approved ELREXFIO® (elranatamab-bcmm) monotherapy for certain adults with relapsed or refractory multiple myeloma. See Safety Info and

7. elrexfio.pfizerpro.com elrexfio.pfizerpro.com/

ELREXFIO Warnings, precautions, and most common adverse reactions seen with ELREXFIO. Review safety data Loading. * ... multiple myeloma; VGPR=very good partial response.

8. ashpublications.org ashpublications.org/blood/article/146/16/1929/546367/Safety-and-efficacy-of-elranatamab-in-patients

Safety and efficacy of elranatamab in patients with relapsed ... Elranatamab elicits deep and rapid heme responses in patients with relapsed AL amyloidosis, including minimal residual disease negativity.

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11269363/

Long‐term survival and safety of elranatamab in patients with ... Long‐term survival and safety of elranatamab in patients with relapsed or refractory multiple myeloma: Update from the MagnetisMM‐3 study

10. labeling.pfizer.com labeling.pfizer.com/ShowLabeling.aspx?id=19669

prescribing information for ELREXFIO ELREXFIO is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, ...