Elranatamab Combinations for Multiple Myeloma

Recruiting at 42 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

120 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to determine the Recommended Phase 2 Dose and clinical benefit of elranatamab in combination with other anti-cancer therapies in participants with multiple myeloma.

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.

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

Elranatamab has shown promising results in clinical trials for treating multiple myeloma, with a 63.6% overall response rate and a median duration of response of 17.1 months. It has been approved in the USA for patients with relapsed or refractory multiple myeloma, demonstrating durable responses and manageable safety. ^{1 2 3 4 5}

Is Elranatamab safe for humans?

Elranatamab has been tested in clinical trials for multiple myeloma, showing manageable safety with no dose-limiting toxicities observed. Some adverse events were reported, including low blood cell counts and cytokine release syndrome (a reaction that can cause fever and flu-like symptoms), but overall, it was considered to have a tolerable safety profile. ^{1 3 4 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 immune system to attack the cancer cells. This mechanism is different from traditional treatments and offers hope for patients with relapsed or refractory multiple myeloma who have tried multiple other therapies. ^{1 3 4 8 9}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

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 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]

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]

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]

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]

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]

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 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]

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]

References

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

Elranatamab: First Approval. [2023]

2. 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]

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

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

4. England pubmed.ncbi.nlm.nih.gov

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

5. United States 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. [2022]

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

Safety issues and management of toxicities associated with new treatments for multiple myeloma. [2022]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy and safety of carfilzomib for the treatment of multiple myeloma: An overview of systematic reviews. [2022]

8. United States 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. [2023]

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

Multiple Myeloma: Clinical Updates From the American Society of Hematology Annual Meeting 2018. [2020]