Elranatamab + Iberdomide for Multiple Myeloma

Recruiting at 30 trial locations

Overseen By Pfizer CT.gov Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Pfizer

Must not be taking: CYP3A4/5 inhibitors

Disqualifiers: Plasma cell leukemia, Cardiovascular diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Assessed for approximately 2 years

87 Participants Needed

Trial Summary

What is the purpose of this trial?

The main purpose of the study is to understand how safe and tolerable is elranatamab when given along with iberdomide. There are 2 parts to this study. Part 1 will look at how safe and tolerable is elranatamab when given with iberdomide. Part 2 will look at the correct amount of this combination that can be given to patients with relapsed or refractory multiple myeloma. Myeloma is a type of cancer that begins in plasma cells (white blood cells that produce antibodies). Refractory means a disease or condition that does not respond to treatment. Relapsed means the return of a disease after a period of improvement. All study medicines are given in cycles that last 28 days. Everyone taking part in this study will receive elranatamab as a shot under the skin. Iberdomide will be taken by mouth once a day for 21 days over a 28-day cycle. Participants will receive study medicine until: * their disease progresses or, * they experience unacceptable side effects or, * they choose to no longer take part in the study. The study will look at the experiences of people receiving the study medicines. This will help see if the study medicines are safe and can be used for multiple myeloma treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot take strong inhibitors or inducers of CYP3A4/5 within 2 weeks before starting the study and during the study.

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

Elranatamab has shown promising results in treating multiple myeloma, with a 63.6% overall response rate and a median duration of response of 17.1 months in patients with relapsed or refractory multiple myeloma. It has been approved in the USA based on its response rate and durability of response, offering hope for patients who have tried multiple other treatments. ^{1 2 3 4 5}

Is the combination of Elranatamab and Iberdomide safe for humans?

The safety of Iberdomide has been evaluated in combination with other drugs for multiple myeloma, showing potential side effects similar to other immunomodulatory drugs, such as pneumonia, sepsis, and renal failure. However, specific safety data for the combination of Elranatamab and Iberdomide is not available in the provided research. ^{6 7 8 9 10}

What makes the drug Elranatamab + Iberdomide unique for treating multiple myeloma?

Elranatamab is a novel drug that works by engaging T cells to attack multiple myeloma cells, specifically targeting BCMA, a protein found on these cancer cells. Iberdomide enhances the immune response and works well with other treatments, making this combination potentially more effective for patients who have already tried multiple other therapies. ^{1 2 3 6 11}

Research Team

Pfizer CT.gov Call Center

Principal Investigator

Pfizer

Eligibility Criteria

This trial is for adults with multiple myeloma that has come back or hasn't improved after treatment. They should have had 1-4 prior treatments including specific drugs, be in good physical condition (ECOG 0-1), and meet certain lab criteria like protein levels in the blood or urine.

Inclusion Criteria

I am fully active or can carry out light work.

Measurable disease based on IMWG criteria as defined by at least 1 of the following: Serum M-protein ≥0.5 g/dL by SPEP, Urinary M-protein excretion ≥200 mg/24 hour by UPEP, Serum immunoglobulin FLC ≥10 mg/dL (≥100 mg/L) AND abnormal serum immunoglobulin kappa to lambda FL ratio (<0.26 or >1.65)

I have been diagnosed with multiple myeloma.

Exclusion Criteria

I do not have plasma cell leukemia, smoldering multiple myeloma, Waldenström's macroglobulinemia, amyloidosis, or POEMS syndrome.

Administration with an investigational product within 30 days preceding the first dose of study intervention

I have heart problems or significant heart disease.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive elranatamab and iberdomide in 28-day cycles until disease progression, unacceptable side effects, or withdrawal

Assessed for approximately 2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

90 days after last dose

Treatment Details

Interventions

• Elranatamab
• Iberdomide

Trial Overview The study tests how safe and effective the combination of Elranatamab (injection) and Iberdomide (oral pill) is for treating multiple myeloma. It's divided into two parts: first to find a safe dose and second to confirm this dose can help patients whose cancer returned or resisted previous treatments.

Participant Groups

Group I: Part 2 Dose Randomization Experimental Treatment 2 Interventions

Randomized elranatamab plus iberdomide

Group II: Part 1 Dose Escalation Experimental Treatment 2 Interventions

Non-randomized elranatamab plus iberdomide

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

Bristol-Myers Squibb

Industry Sponsor

Trials

2,731

Recruited

4,127,000+

Headquarters

New York City, USA

Known For

Oncology & Cardiovascular

Top Products

Eliquis, Opdivo, Revlimid, Orencia

Christopher Boerner

Bristol-Myers Squibb

Chief Executive Officer since 2023

PhD in Business Administration from the Haas School of Business, University of California, Berkeley; BA in Economics and History from Washington University in St. Louis

Deepak L. Bhatt

Bristol-Myers Squibb

Chief Medical Officer since 2024

MD from Yale University; MSc in Clinical Epidemiology from the University of Pennsylvania

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]

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]

Isatuximab (anti-CD38) and F50067 (anti-CXCR4) showed promising results as monotherapies in treating multiple myeloma, with overall response rates of 66.7% and 32%, respectively, based on a review of 39 studies involving 1906 patients.

Combination therapies using Isatuximab with lenalidomide and dexamethasone achieved a clinical benefit rate of 83%, while Indatuximab Ravtansine showed response rates of 78% and 79% when combined with these agents, indicating that mAbs can enhance treatment efficacy when used alongside traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Investigational Monoclonal Antibodies in the Treatment of Multiple Myeloma: A Systematic Review of Agents under Clinical Development. Iftikhar, A., Hassan, H., Iftikhar, N., 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]

Iberdomide combined with dexamethasone demonstrated meaningful clinical activity in heavily pretreated patients with relapsed or refractory multiple myeloma, achieving an overall response rate of 32% in the dose-escalation cohort and 26% in the dose-expansion cohort, indicating its potential effectiveness even in difficult-to-treat cases.

The treatment was generally safe, with a recommended phase 2 dose established at 1.6 mg, although some patients experienced serious adverse events, including neutropenia and infections, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicentre, multicohort, open-label, phase 1/2 trial. Lonial, S., Popat, R., Hulin, C., et al.[2022]

Multiple myeloma remains an incurable disease with increasing incidence, and while current treatments using proteasome inhibitors and immunomodulatory drugs have improved outcomes, many patients still experience relapses and resistance.

Iberdomide, a new drug with high specificity for the Ikaros and Aiolos proteins, represents a promising direction in developing more targeted therapies for multiple myeloma, potentially improving treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review on the treatment of multiple myeloma with small molecular agents in the past five years. Zhang, Z., Liu, X., Zhao, L., et al.[2022]

A comprehensive analysis of adverse event reports for thalidomide, lenalidomide, and pomalidomide revealed significant safety signals, including thalidomide's association with cardiac disorders and lenalidomide's gastrointestinal issues, highlighting the need for careful monitoring in patients.

Pomalidomide was found to have a lower risk of venous thromboembolism compared to thalidomide and lenalidomide, making it a potentially safer option for patients, especially those with renal insufficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-marketing safety of immunomodulatory drugs in multiple myeloma: A pharmacovigilance investigation based on the FDA adverse event reporting system. Jiang, T., Su, H., Li, Y., et al.[2022]

Four new agents have been approved for treating relapsed/refractory multiple myeloma, including bortezomib, lenalidomide, thalidomide, and liposomal doxorubicin, but there is no standard treatment, making personalized therapy essential.

New agents like carfilzomib and pomalidomide are being studied for their effectiveness and side effects, highlighting the importance of understanding treatment-related adverse events in choosing the best therapy for individual patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-related adverse events in patients with relapsed/refractory multiple myeloma. Vij, R.[2017]

Over 80% of patients with multiple myeloma experience osteolytic bone disease, which significantly raises the risk of skeletal-related events like fractures and spinal cord compression.

Bisphosphonates, particularly pamidronate and zoledronic acid, are effective in inhibiting osteoclastic activity to manage bone disease in multiple myeloma, but they carry risks of renal toxicity and osteonecrosis of the jaw, highlighting the need for careful management and ongoing research into optimal treatment duration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trials of bisphosphonates in multiple myeloma. Mahindra, A., Pozzi, S., Raje, N.[2018]

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. Switzerland pubmed.ncbi.nlm.nih.gov

Investigational Monoclonal Antibodies in the Treatment of Multiple Myeloma: A Systematic Review of Agents under Clinical Development. [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

Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicentre, multicohort, open-label, phase 1/2 trial. [2022]

7. France pubmed.ncbi.nlm.nih.gov

A review on the treatment of multiple myeloma with small molecular agents in the past five years. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Post-marketing safety of immunomodulatory drugs in multiple myeloma: A pharmacovigilance investigation based on the FDA adverse event reporting system. [2022]

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

Treatment-related adverse events in patients with relapsed/refractory multiple myeloma. [2017]

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

Clinical trials of bisphosphonates in multiple myeloma. [2018]

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

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