T-cell Engager vs Stem Cell Transplant for Multiple Myeloma

(FASTER Trial)

Recruiting at 5 trial locations

Overseen By Sarah Cannon Development Innovations, LLC

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: SCRI Development Innovations, LLC

Must be taking: Lenalidomide, Anti-CD38 mAb

Must not be taking: Anti-BCMA, Epigenetic therapy

Disqualifiers: CNS involvement, Active malignancies, COPD, 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: Unknown

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine which treatment is more effective for individuals with newly diagnosed multiple myeloma who have already received initial therapy. It compares two approaches: one using the medications elranatamab (a T-cell engager) and daratumumab, and the other involving a stem cell transplant followed by lenalidomide and daratumumab. Participants should have been diagnosed with multiple myeloma within the past year and have completed initial induction therapy with a partial response. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to significant advancements in multiple myeloma treatment.

Will I have to stop taking my current medications?

The trial requires a 'washout period' (time without taking certain medications) for some treatments before starting the study. Specifically, you must stop PI therapy, IMiD agent therapy, and anti-CD38 monoclonal therapy for 14 days, and corticosteroids for 7 days before participating.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies found that combining elranatamab and daratumumab had a manageable safety profile for people with newly diagnosed multiple myeloma. This indicates that side effects were generally not severe and could be managed with standard care. Research has also shown that these treatments had a high response rate, meaning they worked well for most patients.

For elranatamab alone, studies in patients with relapsed or refractory multiple myeloma (a form of cancer that does not respond to treatment or returns after treatment) found that the treatment was well-tolerated, with most side effects being mild to moderate.

The treatment involving autologous stem cell transplant (ASCT) followed by lenalidomide and daratumumab is a well-established approach. ASCT uses a patient's own stem cells, reducing the risk of severe immune reactions. Lenalidomide and daratumumab are also commonly used in multiple myeloma and have known safety profiles, meaning doctors are familiar with their side effects and how to manage them.

In summary, both treatment options in the trial have shown to be reasonably safe in past studies, with manageable side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the treatments in this trial for multiple myeloma because they offer new approaches to tackling the disease. Unlike traditional therapies that often rely heavily on autologous stem cell transplantation (ASCT), Elranatamab is a T-cell engager that activates the body's own immune cells to target and destroy cancer cells. This mechanism could potentially lead to more precise targeting of myeloma cells with fewer side effects. Additionally, Elranatamab is administered subcutaneously, which could be more convenient and less invasive than intravenous therapies. These innovations could provide patients with more effective and patient-friendly treatment options.

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

Research has shown that combining elranatamab and daratumumab, which participants in Arm A of this trial may receive, holds promise for treating multiple myeloma, a type of blood cancer. One study found that about 92% of patients responded well to this combination, with many experiencing significant cancer reduction. Elranatamab alone has also proven effective, with about 62% of patients responding well in real-world settings. Additionally, treatments that include a stem cell transplant followed by lenalidomide and daratumumab, as studied in Arm B of this trial, are well-established and often lead to good results. These findings suggest that both treatment options could effectively manage multiple myeloma. ^{2 6 7 8 9}

Who Is on the Research Team?

Henning Schade, MD

Principal Investigator

Colorado Blood Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed multiple myeloma who've had prior therapy and responded partially. They must have measurable disease, be fit (ECOG 0-1), able to undergo stem cell transplant, and not need recent blood transfusions. It's not suitable for those outside these criteria or ineligible by institutional policy.

Inclusion Criteria

I've had initial treatment with specific drugs and saw improvement.

My cancer can be measured by medical tests.

My cancer has a trackable genetic marker for monitoring.

Exclusion Criteria

Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients

Minimum washout periods for prior therapy

I do not have myelodysplastic syndrome or other active cancers, except for MM.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Consolidation

Participants receive either elranatamab and daratumumab or undergo ASCT followed by lenalidomide and daratumumab

12 weeks

Weekly visits for elranatamab and daratumumab; ASCT according to standard of care

Maintenance 1

Participants receive maintenance treatment with either elranatamab and daratumumab or lenalidomide and daratumumab

48 weeks

Monthly visits

Maintenance 2

Participants with MRD negativity continue with monotherapy maintenance treatment

48 weeks

Monthly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Autologous Stem Cell Transplantation
• Daratumumab
• Elranatamab
• Lenalidomide

Trial Overview The study compares two treatments post-induction: Arm A uses elranatamab plus daratumumab as consolidation/maintenance, while Arm B involves a stem cell transplant followed by lenalidomide and daratumumab treatment. The goal is to see which method better eliminates residual disease in the bone marrow.

How Is the Trial Designed?

Group I: Arm B1 (Late Intensification) Experimental Treatment 2 Interventions

Participants randomized to Arm B that have MRD positivity after Maintenance 1 will receive Elranatamab in combination with Daratumumab for three 28-day cycles as consolidation, followed by Elranatamab in combination with Daratumumab for additional twelve 28-day cycles of maintenance treatment in the Late Intensification portion of the study.

Group II: Arm A1 (Late Intensification) Experimental Treatment 3 Interventions

Participants randomized to Arm A that have MRD positivity after Maintenance 1 will undergo ASCT according to standard of care institutional practices followed by twelve 28-day cycles of maintenance treatment with Lenalidomide and Daratumumab in the Late Intensification portion of the study.

Group III: Arm A (Elranatamab + Daratumumab) Experimental Treatment 2 Interventions

Participants will receive step up dosing of Elranatamab subcutaneously in first cycle followed by weekly dosing for the remainder of the cycle 1. In cycle 2 and 3, elranatamab will be administered every two weeks (Consolidation portion). This will be followed by elranatamab every 4 weeks for 12 cycles in the Maintenance 1 portion. Daratumumab will be given subcutaneously at a fixed dose every 4 weeks starting at Cycle 2 and 3 of Consolidation and for 12 cycles in the Maintenance 1 portion of the study. After completion of Maintenance 1, participants with MRD negativity will receive Elranatamab monotherapy every 4 weeks for additional 12 cycles in Maintenance 2 portion. Participants with MRD positivity will proceed to Arm A1. Participants will undergo therapy in the assigned arm until disease progression, permanent discontinuation (irrespective of reason), death or completion of planned therapy. Cycles will be 28 days. Consolidation consists of 3 cycles; Maintenance 1 consists of 12

Group IV: Arm B (ASCT + lenalidomide/daratumumab) Active Control 3 Interventions

Participants will undergo ASCT according to standard of care institutional practices in the Consolidation portion of the study followed by twelve 28-day cycles of Lenalidomide and Daratumumab in the Maintenance 1 portion. After completion of Maintenance 1, participants with MRD negativity will receive Lenalidomide monotherapy for additional 12 cycles in Maintenance 2 portion. Participants with MRD positivity will proceed to Arm B1. Participants will undergo therapy in the assigned arm until disease progression, permanent discontinuation (irrespective of reason), death or completion of planned therapy. Cycles will be 28 days. Consolidation consists of ASCT; Maintenance 1 consists of 12 cycles; Maintenance 2 consists of 12 cycles. Up to 50 participants will be enrolled to this arm.

Who Is Running the Clinical Trial?

SCRI Development Innovations, LLC

Lead Sponsor

Trials

193

Recruited

13,800+

coMMit, Myeloma Trials, Innovated

Collaborator

Trials

2

Recruited

380+

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

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e19519

Real-world outcomes of patients with multiple myeloma ... About half (44%) were BCMA-exposed. The overall response rate (ORR) was 62%, mPFS was 6.8 months, and median overall survival (OS) was 16.23 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12297639/

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. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/4735/533690/Frailty-and-Outcomes-after-Bispecific-T-Cell

Frailty and Outcomes after Bispecific T-Cell Engager Therapy ... With a median follow up of 7.3 months (range 3.7-12.2), median PFS and OS for the entire patient population was 5.6 (2.7-10.4) and 7.4 (3.9-12.6) ...

4. nature.com nature.com/articles/s41408-024-01139-y

Bispecific antibodies in the treatment of multiple myeloma The overall response rate was 68% with VGPR or better in 54% patients, and CR of 36% at doses of ≥40 mg Q3W in the dose expansion cohort [68].

5. cancernursingtoday.com cancernursingtoday.com/post/do-racial-disparities-influence-t-cell-engager-outcomes-in-patients-with-relapsed-or-refractory-multiple-myeloma

Do Racial Disparities Influence T-Cell Engager Outcomes ... T-cell engagers have helped to prolong survival in patients with RRMM, “with response rates in heavily pretreated patients approaching ...

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

Long‐term survival and safety of elranatamab in patients with ... Long‐term survival and safety of elranatamab in patients with relapsed or refractory multiple myeloma: Update from the MagnetisMM‐3 study

7. astctjournal.org astctjournal.org/article/S2666-6367(24)00779-6/fulltext

Efficacy and Safety of Bispecific T-Cell Engagers in ... Efficacy and safety of bispecific T-cell engagers in relapsed/refractory multiple myeloma: a real-world data-based case-controlled study.

8. ashpublications.org ashpublications.org/hematology/article/2023/1/348/506446/Managing-side-effects-guidance-for-use-of

Managing side effects: guidance for use of immunotherapies ... Efficacy and safety of elranatamab in patients with relapsed/refractory multiple myeloma naïve to B-cell maturation antigen (BCMA)-directed ...

9. cancerci.biomedcentral.com cancerci.biomedcentral.com/articles/10.1186/s12935-023-03045-y

Safety and efficacy of T-cell-redirecting bispecific antibodies ... In an era with several emerging promising treatments for MM, BsAbs have achieved a high ORR and tolerable AEs in heavily pretreated patients.