Elranatamab + Daratumumab + Lenalidomide for Multiple Myeloma

(MagnetisMM-6 Trial)

Recruiting at 71 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, Waldenströms, Plasma cell leukemia, 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

966 Participants Needed

Trial Summary

What is the purpose of this trial?

Elranatamab is a bispecific antibody: binding of elranatamab to CD3-expressing T-cells and BCMA-expressing multiple myeloma cells causes targeted T-cell-mediated cytotoxicity. The main purpose of the study is to evaluate if the combination of Elranatamab, Daratumumab and Lenalidomide or Elranatamab and Lenalidomide offers superior clinical benefit compared with the combination of Daratumumab, Lenalidomide and Dexamethasone in people with multiple myeloma. There are 2 parts to this study. Part 1 will characterize the safety and tolerability of elranatamab in combination with daratumumab and lenalidomide or in combination with lenalidomide and will identify the optimal dose(s) of the combination regimen. Part 2 of the study will evaluate the minimal residual disease (MRD) negativity rate and the progression free survival (PFS) of the combination of elranatamab, daratumumab, and lenalidomide or elranatamab and lenalidomide compared with the combination of daratumumab, lenalidomide, and dexamethasone in participants with newly diagnosed transplant-ineligible multiple myeloma.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you must stop taking your current medications. However, if you have relapsed/refractory multiple myeloma, you should not have had BCMA-directed or anti-CD38-directed therapy within 6 months before the trial. If you have newly diagnosed multiple myeloma, you should not have had previous systemic treatment for multiple myeloma, except for a short course of corticosteroids.

What data supports the idea that Elranatamab + Daratumumab + Lenalidomide for Multiple Myeloma is an effective treatment?

The available research shows that combining Daratumumab with Lenalidomide and Dexamethasone is effective for treating multiple myeloma. In one study, the combination resulted in an 81% overall response rate, meaning most patients saw their cancer improve. Another study found that adding Daratumumab to Lenalidomide and Dexamethasone significantly improved the time patients lived without their cancer getting worse compared to using Lenalidomide and Dexamethasone alone. These results suggest that this combination is a strong option for treating multiple myeloma. ^{1 2 3 4 5}

What safety data is available for the treatment of Elranatamab, Daratumumab, and Lenalidomide in multiple myeloma?

The safety data for the combination of Daratumumab, Lenalidomide, and Dexamethasone in multiple myeloma shows that common grade 3-4 adverse events include neutropenia, thrombocytopenia, and anemia. Infusion-related reactions were also noted, mostly during the first infusions and were generally mild to moderate. The combination was well tolerated and consistent with the safety profiles observed with Lenalidomide/Dexamethasone or Daratumumab monotherapy. Additionally, non-hematologic adverse events such as peripheral sensory neuropathy and infections were reported. The treatment has been shown to be effective and safe in relapsed/refractory multiple myeloma patients. ^{1 2 4 5 6}

Is the drug combination of Daratumumab, Dexamethasone, Elranatamab, and Lenalidomide promising for treating multiple myeloma?

Yes, the drug combination is promising for treating multiple myeloma. Daratumumab, when combined with Lenalidomide and Dexamethasone, has shown to be effective in producing rapid and lasting responses in patients. It works by helping the immune system target and kill myeloma cells. This combination has been well-tolerated and has improved survival rates in patients with relapsed or difficult-to-treat multiple myeloma. ^{1 5 7 8 9}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for adults with newly diagnosed multiple myeloma who can't have a transplant, due to age or other health issues. It's also open to those who've had up to two prior treatments but haven't used certain myeloma drugs in the last six months. Participants should be able to perform daily activities with ease (ECOG ≤2) and not be pregnant.

Inclusion Criteria

I can take care of myself but might not be able to do heavy physical work.

I have multiple myeloma and have had 1-2 prior treatments or am ineligible for a transplant.

My blood or urine tests show signs of my disease according to specific criteria.

Exclusion Criteria

I haven't taken any experimental drugs or vaccines within the last 30 days.

I have been diagnosed with Waldenström's Macroglobulinemia.

I have been diagnosed with a condition where abnormal proteins are in my blood.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Part 1: Safety and Dose Finding

Characterize the safety and tolerability of elranatamab in combination with daratumumab and lenalidomide or in combination with lenalidomide and identify the optimal dose(s) of the combination regimen

Varies

Part 2: Efficacy Evaluation

Evaluate the minimal residual disease (MRD) negativity rate and the progression free survival (PFS) of the combination treatments

Up to 79 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Daratumumab
• Dexamethasone
• Elranatamab
• Lenalidomide

Trial Overview Researchers are testing if Elranatamab combined with Daratumumab and Lenalidomide works better than the standard combo of Daratumumab, Lenalidomide, and Dexamethasone for multiple myeloma. The study has two parts: first finding a safe dose mix, then comparing how well each treatment prevents disease progression.

Participant Groups

Group I: Part 2: Randomized Arm A: Elranatamab + Lenalidomide Experimental Treatment 2 Interventions

Group II: Part 2 Randomized Arm A: Elranatamab + Daratumumab + Lenalidomide Experimental Treatment 3 Interventions

Group III: Part 1: Elranatamab + Lenalidomide Experimental Treatment 2 Interventions

Group IV: Part 1, Multiple Dose Levels, Elranatamab + Daratumumab + Lenalidomide Experimental Treatment 3 Interventions

Group V: Part 1, Dose Level 1: Elranatamab + Daratumumab + Lenalidomide Experimental Treatment 3 Interventions

Group VI: Part 2 Randomized Arm B: Daratumumab + Lenalidomide + 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 combined with lenalidomide and dexamethasone showed an impressive overall response rate of 81% in patients with relapsed/refractory multiple myeloma, indicating its efficacy in this challenging patient population.

The treatment was well tolerated, with no dose-limiting toxicities observed and manageable infusion-related reactions, suggesting a favorable safety profile consistent with previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma. Plesner, T., Arkenau, HT., Gimsing, P., et al.[2022]

In the phase 3 MAIA trial involving 737 patients, the combination of daratumumab, lenalidomide, and dexamethasone significantly improved both progression-free survival (not reached vs. 34.4 months in the control group) and overall survival (hazard ratio 0.68) in patients with newly diagnosed multiple myeloma who were ineligible for stem-cell transplantation.

The safety profile of the treatment was consistent with previous findings, with no new safety concerns identified, although higher rates of neutropenia and pneumonia were observed in the daratumumab group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial. Facon, T., Kumar, SK., Plesner, T., et al.[2021]

Daratumumab, a monoclonal antibody targeting CD38, has shown significant anti-myeloma activity through various mechanisms, including direct apoptosis and immune system modulation, making it a key treatment for relapsed-refractory multiple myeloma (RRMM).

Clinical trials, such as CASTOR and POLLUX, demonstrated that daratumumab in combination with other therapies (like bortezomib and lenalidomide) significantly improves overall response rates and progression-free survival compared to standard treatments, leading to its approval and integration into clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab for the Management of Newly Diagnosed and Relapsed/Refractory Multiple Myeloma: Current and Emerging Treatments. Offidani, M., Corvatta, L., Morè, S., et al.[2021]

Daratumumab, when combined with lenalidomide and dexamethasone (DRd) or bortezomib and dexamethasone (DVd), showed an overall response rate of 80% in 171 heavily treated patients with relapsed/refractory multiple myeloma, indicating its efficacy in this challenging patient population.

Patients receiving the DRd combination experienced better progression-free survival (PFS) compared to those on DVd, with PFS rates of 84% and 77%, respectively, while the treatment was generally safe, with common side effects including neutropenia and infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab combined with dexamethasone and lenalidomide or bortezomib in relapsed/refractory multiple myeloma (RRMM) patients: Report from the multiple myeloma GIMEMA Lazio group. Fazio, F., Franceschini, L., Tomarchio, V., et al.[2022]

In a study of 162 multiple myeloma patients who received daratumumab, combining it with lenalidomide (DRd) showed no significant difference in progression-free survival (PFS) compared to combining it with pomalidomide (DPd) for those previously treated with lenalidomide.

Both treatment combinations (DRd and DPd) were found to be effective options for patients with relapsed/refractory multiple myeloma, indicating that daratumumab with lenalidomide remains a viable treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab-lenalidomide and daratumumab-pomalidomide in relapsed lenalidomide-exposed or refractory multiple myeloma. Alhaj Moustafa, M., Parrondo, R., Abdulazeez, MF., et al.[2023]

Daratumumab received conditional marketing authorization in the EU for treating relapsed and refractory multiple myeloma, showing an overall response rate of 29.2% in heavily pre-treated patients, indicating its efficacy as a monotherapy.

The drug was later approved for use in combination with lenalidomide and dexamethasone or bortezomib and dexamethasone, demonstrating improved progression-free survival in patients who had received at least one prior therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

EMA Review of Daratumumab for the Treatment of Adult Patients with Multiple Myeloma. Tzogani, K., Penninga, E., Schougaard Christiansen, ML., et al.[2020]

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]

Combining lenalidomide with daratumumab significantly enhances the ability of the immune system to kill multiple myeloma cells, as shown in assays using both cell lines and primary patient cells.

The synergy between lenalidomide and daratumumab was particularly evident in the bone marrow environment of multiple myeloma patients, suggesting that this combination could be a powerful treatment strategy in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Towards effective immunotherapy of myeloma: enhanced elimination of myeloma cells by combination of lenalidomide with the human CD38 monoclonal antibody daratumumab. van der Veer, MS., de Weers, M., van Kessel, B., et al.[2021]

In the phase III ELOQUENT-2 trial involving adults with relapsed multiple myeloma, elotuzumab combined with lenalidomide and dexamethasone significantly improved progression-free survival and overall response rates compared to the standard treatment alone.

The addition of elotuzumab did not negatively affect health-related quality of life and had a manageable safety profile, with the most common serious side effects being blood-related issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab: A Review in Relapsed and/or Refractory Multiple Myeloma. Lamb, YN.[2019]

References

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

Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma. [2022]

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

Daratumumab, lenalidomide, and dexamethasone versus lenalidomide and dexamethasone alone in newly diagnosed multiple myeloma (MAIA): overall survival results from a randomised, open-label, phase 3 trial. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Daratumumab for the Management of Newly Diagnosed and Relapsed/Refractory Multiple Myeloma: Current and Emerging Treatments. [2021]

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

Daratumumab combined with dexamethasone and lenalidomide or bortezomib in relapsed/refractory multiple myeloma (RRMM) patients: Report from the multiple myeloma GIMEMA Lazio group. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Daratumumab-lenalidomide and daratumumab-pomalidomide in relapsed lenalidomide-exposed or refractory multiple myeloma. [2023]

6. England pubmed.ncbi.nlm.nih.gov

EMA Review of Daratumumab for the Treatment of Adult Patients with Multiple Myeloma. [2020]

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

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

8. Italy pubmed.ncbi.nlm.nih.gov

Towards effective immunotherapy of myeloma: enhanced elimination of myeloma cells by combination of lenalidomide with the human CD38 monoclonal antibody daratumumab. [2021]

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

Elotuzumab: A Review in Relapsed and/or Refractory Multiple Myeloma. [2019]