Elranatamab for Multiple Myeloma

(EMBRACE Trial)

Recruiting at 4 trial locations

Overseen By Daryl Solomon

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ontario Clinical Oncology Group (OCOG)

Must not be taking: Chemotherapy, Anti-MM drugs

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

Duration: 24 months

40 Participants Needed

Trial Summary

What is the purpose of this trial?

A phase II study of single agent elranatamab in patients with relapsed and/or refractory multiple myeloma (MM) who have previously received at least three classes of therapeutic agents and are refractory to the last line of treatment. The primary objective of this study is to improve the tolerability and safety of elranatamab in patients with relapsed and/or refractory multiple myeloma by evaluating an outpatient and intermittent dosing strategy.

Do I need to stop my current medications to join the trial?

The trial requires that you stop taking any chemotherapeutic or anti-multiple myeloma drugs within the last 28 days or 5 half-lives before joining. You also need to stop any cancer treatments, including certain steroids, within 14 days before joining.

What data supports the effectiveness of the drug Elranatamab for 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 achieved a response, and the drug demonstrated durable responses and manageable safety, offering hope for patients 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}

How is the drug Elranatamab unique in 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. It is administered subcutaneously and has shown promising results in patients who have already undergone multiple treatments, offering a new option for those with relapsed or refractory multiple myeloma. ^{1 2 3 7 8}

Research Team

Hira Mian, MD

Principal Investigator

McMaster University

Jim Wright, MD

Principal Investigator

OCOG - McMaster University

Eligibility Criteria

This trial is for people with multiple myeloma, a type of blood cancer, who have tried at least three different treatments without success and are not responding to their current treatment. Participants will receive the drug as outpatients and must be able to visit the clinic for doses.

Inclusion Criteria

Measurable disease based on IMWG criteria: Serum M-protein ≥ 0.5 g/dl, Urine M-protein excretion ≥ 200 mg/24 h, Serum-free light chains (FLC) assay: Involved FLC level ≥ 10 mg/dl AND an abnormal serum-free light chain ratio (< 0.26 or > 1.65) only for patients without measurable serum or urine M protein

I can perform daily activities with minimal assistance.

I have been treated with drugs from three specific classes for my condition.

Exclusion Criteria

Any serious and/or unstable pre-existing medical, psychiatric disorder, or other conditions that could interfere with the patient's safety, obtaining informed consent or compliance to the study procedures

I have a blood condition that is not active cancer.

Laboratory parameters: ANC ≤ 1.0 x 109 /L, Platelet count ≤ 25 x 109 /L, Hemoglobin ≤ 8.0 g/dL, Serum AST and ALT > 2.5 x upper limit of normal, Creatinine clearance < 30 mL/min, Total bilirubin > 2.0 x ULN

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SC administration of elranatamab with varying dosing intervals based on treatment cycles

24 months

Weekly visits for Cycle 1, bi-weekly for Cycles 2-3, monthly for Cycles 4-12, and every 8 weeks for Cycles 13+ if criteria met

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Treatment Details

Interventions

• Elranatamab

Trial Overview The study is testing elranatamab injections in an outpatient setting with intermittent dosing. The goal is to see if this approach makes the drug easier to tolerate and safer for patients who have relapsed or are resistant to other treatments.

Participant Groups

Group I: Elranatamab injection Experimental Treatment 1 Intervention

The administration of two step-up elranatamab doses (12 mg and 32 mg) and full dose 76 mg. The dosing interval for the first Cycle (each cycle q28 days) is every week. Cycles 2-3, the dosing interval increases to q2weeks. Cycles 4-12, the dosing interval increases to q4weeks. Cycles 13+, further dosing interval increases to q8weeks will be scheduled if a participant meets criteria for IMWG complete response (CR) in Cycle 12 (bone marrow required at Cycle 12 to confirm). If a participant does not meet CR criteria at Cycle 12, they will be continued on Q4W dosing.

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?

Ontario Clinical Oncology Group (OCOG)

Lead Sponsor

Trials

65

Recruited

42,000+

Pfizer

Industry 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]

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 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]