Elranatamab for Multiple Myeloma

Recruiting in Palo Alto (17 mi)

+152 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Pfizer

Must be taking: Anti-CD38, Lenalidomide

Must not be taking: BCMA therapy, CD3 therapy

Disqualifiers: Smoldering MM, Plasma cell leukemia, Amyloidosis, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

The purpose of this study is to learn about the study medicine called elranatamab.This study aims to compare elranatamab to other medicines for the treatment of MM (a type of cancer). This study is seeking participants who: * Are 18 years of age or older and have MM. * Have received treatments before for MM. * Have MM that has returned or not responded to their most recent treatment. Half of the participants will receive elranatamab. The other half of participants will receive a combination therapy selected by the study doctor. The selected combination therapy will include 2 to 3 different medicines commonly used to treat MM. Elranatamab will be given as a shot under the skin at the study clinic about once a week. This may change to a smaller number of shots later in the study. The medicines in the combination therapy will be taken by mouth (at home or at the study clinic) AND will be given either as: * a shot under the skin at the study clinic * through a needle in the vein at the study clinic The number of times these medicines will be taken depends on what combination therapy the study doctor selects. Participants may continue to receive elranatamab or a combination therapy until their MM is no longer responding. The study team will see how each participant is doing with the study treatment during regular visits at the study clinic. The study team will continue to follow-up with participants after study treatment with telephone contacts (or visits). The study will compare the experiences of people receiving elranatamab to those people receiving a combination therapy. This will help learn about the safety and how effective elranatamab is.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It is best to discuss this with the study doctor to understand how your current treatments might interact with the trial.

What data supports the effectiveness of the drug Elranatamab for treating multiple myeloma?

Elranatamab has shown promising results in clinical trials for multiple myeloma, with a significant number of patients responding to the treatment. In the MagnetisMM-1 trial, 63.6% of patients experienced a positive response, and the drug demonstrated durable responses and manageable safety, offering hope for those with relapsed or refractory multiple myeloma. ^{1 2 3 4 5}

Is Elranatamab safe for humans?

Elranatamab has been tested in clinical trials for multiple myeloma, and no dose-limiting toxicities (serious side effects that prevent increasing the dose) were observed. Some side effects included low blood cell counts and cytokine release syndrome (a reaction that can cause fever and flu-like symptoms), but overall, the safety was considered manageable. ^{1 2 3 6 7}

What makes the drug Elranatamab unique for treating multiple myeloma?

Elranatamab is unique because it is a bispecific antibody that targets both BCMA on myeloma cells and CD3 on T cells, activating the T cells to attack the cancer cells. It is administered subcutaneously and has shown promising results in patients who have already undergone multiple other treatments, offering a new option for those with relapsed or refractory multiple myeloma. ^{1 2 3 7 8}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for adults with Multiple Myeloma (MM) that has returned or hasn't responded after treatment, including anti-CD38 antibody and lenalidomide. Participants must have had 1 to 4 prior MM treatments, meet specific lab value criteria, not be pregnant or breastfeeding, and agree to use contraception.

Inclusion Criteria

You are not pregnant or breastfeeding and are okay with using birth control.

My last cancer treatment did not work according to IMWG standards.

My last cancer treatment did not work as expected.

Exclusion Criteria

I do not have any ongoing serious infections.

I haven't had any cancer except for certain skin cancers or localized cancers that were treated, in the last 3 years.

I cannot undergo the standard treatment recommended by my doctor.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive elranatamab or a combination therapy until their MM is no longer responding

Up to approximately 5 years

Weekly visits initially, with potential reduction in frequency

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 35 days after last administration of study intervention

Telephone contacts or visits

Treatment Details

Interventions

• Elranatamab (Monoclonal Antibodies)

Trial Overview The study compares elranatamab—a new medication given as a weekly shot—with a combination of standard MM therapies chosen by the doctor. The goal is to evaluate elranatamab's safety and effectiveness against these common treatments.

Participant Groups

Group I: Elranatamab Experimental Treatment 1 Intervention

Participants will receive elranatamab monotherapy

Group II: Investigator's Choice Active Control 5 Interventions

Participants will receive either Elotuzumab, Pomalidomide and Dexamethasone (EPd), or Pomalidomide, Bortezomib and Dexamethasone (PVd), or Carfilzomib and Dexamethasone (Kd)

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

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]

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]

In a phase II study involving 15 patients with relapsed multiple myeloma, the combination of elotuzumab with carfilzomib, lenalidomide, and dexamethasone (Elo-KRd) showed a 46.7% rate of achieving very good partial response (≥VGPR) after 4 cycles of treatment, indicating significant efficacy in a challenging patient population.

The treatment was well-tolerated with no new safety concerns reported, and the overall response rate was 80%, suggesting that Elo-KRd is a promising option for patients with high-risk and lenalidomide-refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Clinical and Correlative Study of Elotuzumab, Carfilzomib, Lenalidomide, and Dexamethasone (Elo-KRd) for Lenalidomide Refractory Multiple Myeloma in First Relapse. Bhutani, M., Foureau, DM., Robinson, M., et al.[2023]

The treatment landscape for multiple myeloma (MM) has significantly improved, with four new drugs approved in 2015 alone, leading to better patient outcomes than seen in any other cancer over the past decade.

Several new investigational agents, such as Isatuximab and marizomib, show promising efficacy in clinical trials, indicating a strong potential for future regulatory approval and further advancements in MM treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New investigational drugs with single-agent activity in multiple myeloma. Rajan, AM., Kumar, S.[2022]

In a review of 20 studies involving 2220 patients with relapsed/refractory multiple myeloma, carfilzomib combinations showed a high overall response rate of 61%, with 29% achieving at least a very good partial response.

Elotuzumab combinations were particularly effective, with a 73% overall response rate and 37% achieving at least a very good partial response, although patients experienced significant nonhematologic adverse events like cardiac issues and pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pooled analysis of the reports of carfilzomib, panobinostat, and elotuzumab combinations in patients with refractory/relapsed multiple myeloma. Liu, L., Zhao, N., Xu, W., et al.[2018]

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]

In the phase 2 MagnetisMM-3 trial, elranatamab demonstrated a confirmed objective response rate of 61.0% in patients with relapsed or refractory multiple myeloma, indicating its efficacy as a treatment option.

The safety profile of elranatamab was manageable, with a reduction in grade 3-4 adverse events when switching from weekly to biweekly dosing, suggesting that this adjustment may enhance long-term safety without affecting treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. Lesokhin, AM., Tomasson, MH., Arnulf, B., et al.[2023]

References

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

Elranatamab: First Approval. [2023]

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

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

3. England pubmed.ncbi.nlm.nih.gov

Elrexfio™ (elranatamab-bcmm): The game-changer in treatment of multiple myeloma. [2023]

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

A Clinical and Correlative Study of Elotuzumab, Carfilzomib, Lenalidomide, and Dexamethasone (Elo-KRd) for Lenalidomide Refractory Multiple Myeloma in First Relapse. [2023]

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

New investigational drugs with single-agent activity in multiple myeloma. [2022]

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

Pooled analysis of the reports of carfilzomib, panobinostat, and elotuzumab combinations in patients with refractory/relapsed multiple myeloma. [2018]

7. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. [2023]