Elranatamab Combinations for Multiple Myeloma

Not currently recruiting at 45 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Pfizer

Disqualifiers: Active infections, Cardiovascular diseases, 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: 32

Duration: approximately 42 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment for multiple myeloma, a type of blood cancer. Researchers are testing elranatamab, a new potential drug, combined with other cancer-fighting drugs to determine the best dose and assess its effectiveness. Two study groups exist: one combines elranatamab with an immunomodulatory drug, and the other with a gamma secretase inhibitor. The trial seeks participants with multiple myeloma that has returned or not responded after at least three different therapy types. Those who have tried these treatments and still show signs of the disease might be suitable candidates. 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 information does not specify if you need to stop taking your current medications. However, if you have taken an investigational drug recently, you may need to wait 30 days or longer before starting 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 patients with multiple myeloma. One study found that 30% of patients achieved a complete response, with no cancer detected in their blood or urine. This suggests the treatment works as intended without unexpected safety issues.

For nirogacestat, studies have consistently demonstrated its safety in treating desmoid tumors. Patients have used it for up to four years, and it has been associated with smaller tumors and health improvements. This long-term safety data is reassuring for its use in clinical trials.

Both treatments have also been studied for other conditions, enhancing understanding of their safety profiles. While any treatment carries risks, these studies suggest that both elranatamab and nirogacestat are generally well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for multiple myeloma, like proteasome inhibitors and immunomodulatory drugs, focus on disrupting the cancer cell's lifecycle. But Elranatamab works differently by targeting BCMA and CD3, acting as a bispecific antibody to directly engage and redirect T-cells to attack myeloma cells. This approach could enhance the immune system's ability to fight the cancer more precisely. Additionally, when combined with Nirogacestat, a gamma secretase inhibitor, Elranatamab's effect could be amplified, potentially offering a more robust response by increasing the availability of BCMA targets on cancer cells. Researchers are excited because these combinations might provide a new, powerful option for patients with fewer side effects than traditional therapies.

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

This trial will evaluate combinations of elranatamab with other treatments for multiple myeloma. Studies have shown that elranatamab can lead to strong and lasting improvements in people with relapsed or hard-to-treat multiple myeloma. About 61% of patients experienced a noticeable improvement, with the treatment preventing the disease from worsening for about 17 months. Additionally, 26% of patients reached a point where cancer was not detectable in their blood or urine.

In this trial, one arm will explore the combination of elranatamab with an immunomodulatory drug, while another arm will test elranatamab with nirogacestat, a gamma secretase inhibitor. Nirogacestat is mainly used for treating desmoid tumors, but research has shown it can significantly slow disease progression and improve patient outcomes. Although primarily used for other types of tumors, its potential benefits in combination treatments for multiple myeloma are being explored due to its effect on tumor growth. ^{1 6 7 8 9}

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 tried at least three other treatments without success, including IMiDs, proteasome inhibitors, and anti-CD38 antibodies. They must have measurable disease indicators and be in good physical condition. People can't join if they've had certain blood disorders or heart issues recently, a stem cell transplant within the last 12 weeks, or any investigational drug use in the past month.

Inclusion Criteria

You have a high level of M-protein in your blood.

My condition did not improve after treatments with IMiD, proteasome inhibitor, and anti-CD38 antibody.

Any side effects from my previous treatments have mostly gone away.

Exclusion Criteria

I have been diagnosed with amyloidosis.

I have previously been treated with BCMA-targeted therapy.

I have been diagnosed with POEMS syndrome.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive elranatamab in combination with other anti-cancer therapies to determine the Recommended Phase 2 Dose and clinical benefit

approximately 42 days

assessed every cycle (each cycle approximately 28 days)

Follow-up

Participants are monitored for safety and effectiveness after treatment

approximately 2 years

assessed every 4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Elranatamab
• Nirogacestat

Trial Overview

The study tests Elranatamab combined with either lenalidomide plus dexamethasone or Nirogacestat to find out the best dose and see how well it works against multiple myeloma. Participants will receive these combinations to assess their effectiveness as cancer treatments.

How Is the Trial Designed?

Group I: Sub-Study B Experimental Treatment 1 Intervention

BCMA-CD3 bispecific antibody + immunomodulatory drug

Group II: Sub-Study A Experimental Treatment 1 Intervention

BCMA-CD3 bispecific antibody + gamma secretase inhibitor

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

Approved in United States as Elrexfio for:

• Relapsed or refractory multiple myeloma

Approved in European Union as Elrexfio for:

• Relapsed or refractory multiple myeloma

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

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]

Triplet regimens including lenalidomide and dexamethasone show effectiveness for high-risk smoldering multiple myeloma, but more long-term follow-up is necessary to confirm these results.

For newly diagnosed multiple myeloma patients, carfilzomib- and daratumumab-based combinations are promising as safe and effective induction treatments, while maintenance therapy with ixazomib significantly prolongs progression-free survival compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multiple Myeloma: Clinical Updates From the American Society of Hematology Annual Meeting 2018. Terpos, E., Ntanasis-Stathopoulos, I.[2020]

Carfilzomib significantly improves progression-free survival, overall survival, and overall response rate in patients with relapsed/refractory multiple myeloma, based on evidence from 14 systematic reviews involving moderate quality data.

However, treatment with carfilzomib is associated with increased risks of cardiovascular events, nephrotoxicity, and serious infections, highlighting the need for careful monitoring and further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of carfilzomib for the treatment of multiple myeloma: An overview of systematic reviews. Georgoulis, V., Haidich, AB., Bougioukas, KI., et al.[2022]

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 introduction of four novel agents (carfilzomib, elotuzumab, daratumumab, and panobinostat) for treating Multiple Myeloma has significantly improved patient outcomes but also introduced new adverse events that require careful management.

This review emphasizes the importance of recognizing and managing the toxicities associated with these new treatments, based on a comprehensive analysis of clinical trials and recent findings presented at major hematology conferences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety issues and management of toxicities associated with new treatments for multiple myeloma. Brioli, A., Mügge, LO., Hochhaus, A., et al.[2022]

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 2 study involving 13 patients with high-risk relapsed/refractory multiple myeloma, the combination of elotuzumab, pomalidomide, carfilzomib, and low-dose dexamethasone showed an overall response rate of 45.4% and a clinical benefit rate of 54.5%, indicating promising efficacy.

The treatment was generally well-tolerated, with manageable adverse events, although 15% of patients experienced severe side effects like lymphopenia, anemia, and pneumonia, suggesting that while effective, careful monitoring is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2 trial of the efficacy and safety of elotuzumab in combination with pomalidomide, carfilzomib and dexamethasone for high-risk relapsed/refractory multiple myeloma. Yashar, D., Spektor, TM., Martinez, D., et al.[2022]

In a phase 2 study involving 46 patients with newly diagnosed multiple myeloma, the quadruplet regimen of elotuzumab, carfilzomib, lenalidomide, and dexamethasone (Elo-KRd) achieved a stringent complete response (sCR) and/or measurable residual disease (MRD)-negativity rate of 58% after 8 cycles, indicating significant efficacy without the need for autologous stem cell transplant (ASCT).

The study demonstrated a 3-year progression-free survival (PFS) rate of 72% overall, and an impressive 92% for patients who achieved MRD-negativity, suggesting that MRD-guided therapy could allow for reduced treatment exposure while maintaining effective outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elotuzumab and Weekly Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma Without Transplant Intent: A Phase 2 Measurable Residual Disease-Adapted Study. Derman, BA., Kansagra, A., Zonder, J., et al.[2023]

ELREXFIO™ (elranatamab-bcmm) is an FDA-approved bispecific antibody that effectively targets both CD3 and BCMA, activating T-cells to attack multiple myeloma cells, which is crucial for patients with relapsed or refractory cases.

Clinical trials, including MagnetisMM-3, have shown significant response rates and long-term tolerability for ELREXFIO, indicating its potential to improve treatment outcomes for patients suffering from this challenging cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Elrexfio™ (elranatamab-bcmm): The game-changer in treatment of multiple myeloma. Rais, T., Khan, A., Riaz, R.[2023]

Citations

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

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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 ...

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ascopubs.org

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Conclusions: Elranatamab demonstrated a manageable safety profile, and SC doses ≥215μg/kg achieved ORR of 75% with CR/sCR rate of 30%. These ...

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The results of this study are consistent with results reported from the phase 1 MagnetisMM-1 study in which a response rate of 64% and a median ...