Elranatamab for Multiple Myeloma

(EMBRACE Trial)

Recruiting at 5 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests elranatamab, a potential new treatment for multiple myeloma, a type of blood cancer. The goal is to determine if this treatment is safe and manageable for individuals whose cancer has returned or stopped responding to standard treatments. The trial seeks participants who have tried several other treatments without success. Those with multiple myeloma that has progressed despite previous therapies might be suitable for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, providing an opportunity to contribute to important findings.

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.

Is there any evidence suggesting that elranatamab is likely to be safe for humans?

Research has shown that elranatamab is safe and generally well-tolerated by people with multiple myeloma, a type of blood cancer. Studies indicate that its side effects can be managed without major problems. In some studies, 30% of patients experienced a complete response, with no detectable signs of cancer. Additionally, no new safety concerns have emerged over time, offering reassurance for those considering this treatment. While discussing any concerns with a healthcare provider is important, current evidence supports its safety for treating multiple myeloma. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Unlike the standard treatments for multiple myeloma, which often include drugs like bortezomib or lenalidomide, elranatamab is unique because it targets a specific protein called BCMA on the surface of myeloma cells. This approach helps the immune system to better recognize and attack the cancer cells. Another key feature is its flexible dosing schedule, which starts with weekly doses and gradually extends to every eight weeks, potentially making it more convenient for patients. Researchers are excited about elranatamab because it offers a new way to combat multiple myeloma by harnessing the immune system more directly and may improve patient outcomes with fewer frequent visits.

What evidence suggests that elranatamab might be an effective treatment for multiple myeloma?

Research has shown that elranatamab, which participants in this trial will receive, may effectively treat relapsed or hard-to-treat multiple myeloma. In one study, 26% of patients achieved a complete response, with no signs of cancer in their blood or urine after treatment. Another study reported a 61% overall response rate, with many patients experiencing significant tumor shrinkage. On average, patients lived for 17.2 months without disease progression, and the median overall survival was 24.6 months. Higher doses of elranatamab and lower levels of a specific protein in the blood correlated with better outcomes. These findings suggest that elranatamab could be a promising option for those with difficult-to-treat multiple myeloma. ^{1 6 7 8 9}

Who Is on the Research Team?

Hira Mian, MD

Principal Investigator

McMaster University

Jim Wright, MD

Principal Investigator

OCOG - McMaster University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

McMaster University

Collaborator

Trials

936

Recruited

2,630,000+

Published Research Related to This Trial

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 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]

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]

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 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 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 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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40826257/

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

2. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-025-14624-9

Comparison of outcomes with elranatamab and real world ... This study aimed to characterise outcomes for real world TCE RRMM patients and to estimate the treatment effect of elranatamab compared to ...

3. elrexfio.com elrexfio.com/results

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 ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7549

A US subgroup analysis from MagnetisMM-3. With a median follow‐up of 33.9 mo, ORR was 61.0%, mPFS was 17.2 mo, and mOS was 24.6 mo. Here we report results for the subgroup of pts ...

5. link.springer.com link.springer.com/article/10.1007/s11523-025-01168-y

Population Exposure–Response Efficacy Analysis of ... The results suggested that higher elranatamab exposure and lower soluble BCMA (sBCMA) were associated with higher probability of achieving ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40713551/

Comparison of outcomes with elranatamab and real world ... This study provides recent real world evidence of poor outcomes in TCE RRMM in the UK. PFS was longer among patients who received ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2021.39.15_suppl.8006

Efficacy and safety of elranatamab (PF-06863135), a B-cell ... Conclusions: Elranatamab demonstrated a manageable safety profile, and SC doses ≥215μg/kg achieved ORR of 75% with CR/sCR rate of 30%. These ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11269363/

Long‐term survival and safety of elranatamab in patients with ... Elranatamab monotherapy continues to improve survival outcomes without new safety signals. ... multiple myeloma: phase 2 MagnetisMM‐3 trial results. Nat Med. 2023 ...

9. nature.com nature.com/articles/s41591-023-02528-9

Elranatamab in relapsed or refractory multiple myeloma 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 ...