Elranatamab for AL Amyloidosis

Overseen By Giada Bianchi

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Brigham and Women's Hospital

Must be taking: Daratumumab, CyBorD

Must not be taking: Investigational agents

Disqualifiers: Stage IIIB Amyloidosis, Active malignancy, HIV, others

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

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

Compensation: Varies

Number of Visits: 5

49 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called elranatamab to determine its safety and effectiveness for people with AL amyloidosis, a condition where abnormal proteins accumulate in tissues and organs. The research aims to find the right dose and assess the drug's effectiveness for those whose disease has returned or did not respond to previous treatments. Individuals who have experienced a return of their AL amyloidosis after at least one prior treatment and are not currently on other experimental therapies might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that elranatamab was safe in earlier studies. People with relapsed AL amyloidosis, a condition where abnormal proteins accumulate in organs, did not experience new side effects when treated with elranatamab. Even those with serious heart issues did not encounter new problems. Reports confirm the treatment's safety, as it doesn't introduce unexpected risks. This supports its use in ongoing studies for similar conditions. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Elranatamab is unique because it represents a new approach to treating AL Amyloidosis. While traditional treatments often focus on managing symptoms or slowing disease progression, Elranatamab is a bispecific antibody that targets specific proteins involved in the disease. This targeted mechanism allows it to home in on the problematic cells more precisely, potentially leading to better outcomes. Additionally, Elranatamab is administered subcutaneously, which could offer a more convenient and less invasive option compared to some existing treatments. Researchers are excited about its potential to provide a more effective and targeted therapy for patients with this challenging condition.

What evidence suggests that elranatamab might be an effective treatment for AL amyloidosis?

Studies have shown that elranatamab can help treat AL amyloidosis, a condition where abnormal proteins accumulate in organs. In earlier research, nine patients with advanced AL amyloidosis showed improvement after using elranatamab, with each patient experiencing some level of benefit. Notably, 67% of these patients had a significant improvement, which is very encouraging. In this trial, participants will receive elranatamab to further evaluate its effectiveness for those with relapsed or difficult-to-treat AL amyloidosis. ^{1 2 4 5 6}

Who Is on the Research Team?

Giada Bianchi, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 with AL amyloidosis that has come back or didn't respond to treatment. They should be relatively active (able to care for themselves) and have certain levels of blood cells, liver, and kidney function. People who've had belantamab mafodotin can join if they stopped due to side effects. Those with chronic hepatitis must have it under control.

Inclusion Criteria

* Participants must meet the following organ and marrow function as defined below: Absolute leukocyte count ≥3,000/mcL , Absolute neutrophil count ≥1,000/mcL, Absolute platelet count ≥75,000/mcL , Direct bilirubin ≤1.5 × institutional upper limit of normal (ULN) AST(SGOT)/ALT(SGPT) ≤3 × institutional ULN, Creatinine: Calculated clearance ≥30 mL/min using Cockcault-Groft equation

I have AL amyloidosis that didn't respond to at least one prior treatment.

My light chain levels have increased by more than 20mg/L.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Phase I Treatment

Participants receive elranatamab with dose escalation to determine the recommended phase 2 dose (RP2D).

6 cycles of 28 days per cycle

Hospitalization for 5-9 days during Cycle 1

Phase II Treatment

Participants receive the RP2D determined in Phase I.

6 cycles of 28 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 72 months

What Are the Treatments Tested in This Trial?

Interventions

• Elranatamab

Trial Overview The study tests elranatamab's safety and effectiveness in those whose AL amyloidosis hasn't improved after previous treatments. It looks at how well patients tolerate the drug and its impact on their disease, especially for those with specific heart conditions and measurable signs of the disease in their blood.

How Is the Trial Designed?

Group I: Elranatamab Dose Schedule Experimental Treatment 1 Intervention

Phase I: Phase I will enroll up to 20 participants. All participants in Phase I will be hospitalized during Cycle 1 dosing. The first 5 participants will be hospitalized for 9 days, and subsequent participants will be hospitalized for 5 days. Elranatamab will be administered subcutaneously at a dose of 12 mg on C1D1, 32 mg on C1D4, and 76 mg on C1D8. Subsequent treatment doses will be 76 mg thereafter. If two or more participants at Level 0 experience DLT, dose will be decreased to Level -1. If 2 or more participants at Level -1 experience DLT, the trial will be discontinued. Phase II: All participants in Phase 2 will receive the RP2D determined in Phase 1. Phase 2 will enroll an additional 29 participants. If RP2D is determined to be Dose Level 0, the treatment schedule will be the same as described in Dose Level 0. If RP2D is determined to be Dose Level -1, the treatment schedule will be the same as described in Dose Level -1.Treatment duration is 6 cycles of 28 days per cycle.

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?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Published Research Related to This Trial

Elranatamab, a bispecific antibody targeting BCMA and CD3, showed significantly higher objective response rates and complete response rates compared to physician's choice of treatment in patients with triple-class exposed/refractory multiple myeloma, based on data from the MagnetisMM-3 trial with 123 participants.

Patients treated with elranatamab also experienced longer progression-free survival and overall survival compared to those receiving physician's choice treatment, indicating its potential as a more effective option for this difficult-to-treat patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A matching-adjusted indirect comparison of the efficacy of elranatamab versus physician's choice of treatment in patients with triple-class exposed/refractory multiple myeloma. Mol, I., Hu, Y., LeBlanc, TW., et al.[2023]

In a study of 10 patients with Her2-positive breast cancer brain metastases, T-DM1 showed promising activity, with 3 patients achieving partial remission and 2 maintaining stable disease for at least 6 months.

The median intracranial progression-free survival (PFS) was 5 months, suggesting that T-DM1 could be a viable systemic therapy option for brain metastases, warranting further investigation despite local treatment remaining the standard of care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of T-DM1 in Her2-positive breast cancer brain metastases. Bartsch, R., Berghoff, AS., Vogl, U., et al.[2019]

In a study of 214 patients with HER2-positive breast cancer brain metastases, trastuzumab emtansine (T-DM1) significantly improved overall survival compared to lapatinib plus capecitabine, with median survival times of 17.7 months versus 9.6 months, respectively.

T-DM1 also demonstrated better outcomes in terms of time to next treatment and real-world progression-free survival, indicating its superior effectiveness in managing this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine vs lapatinib and capecitabine in HER2-positive metastatic breast cancer brain metastases: A real-world study. Sanglier, T., Shim, J., Lamarre, N., et al.[2023]

In a retrospective study of 69 female patients with hormone receptor-positive, HER2-negative metastatic breast cancer, abemaciclib demonstrated effectiveness as both a monotherapy and in combination with endocrine therapy, aligning with previous clinical trial results.

The median duration of abemaciclib treatment was 7.7 months, with 86% of patients discontinuing treatment mainly due to disease progression, indicating that while effective, the drug is often used in heavily pretreated patients with advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Observational study of HR+/HER2- metastatic breast cancer patients treated with abemaciclib in Spain in the Named Patient Use Program (AbemusS). Blanch, S., Gil-Gil, JM., Arumí, M., et al.[2023]

In a study of 398 patients with HER2-positive breast cancer and brain metastases, trastuzumab emtansine (T-DM1) demonstrated a best overall response rate of 21.4% and a clinical benefit rate of 42.9%, indicating its potential effectiveness in this challenging population.

The median progression-free survival was 5.5 months and overall survival was 18.9 months, with T-DM1 showing a tolerable safety profile, although nervous system adverse events were more common in patients with brain metastases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab emtansine (T-DM1) in patients with HER2-positive metastatic breast cancer and brain metastases: exploratory final analysis of cohort 1 from KAMILLA, a single-arm phase IIIb clinical trial☆. Montemurro, F., Delaloge, S., Barrios, CH., et al.[2021]

Citations

1. ashpublications.org ashpublications.org/blood/article/146/16/1929/546367/Safety-and-efficacy-of-elranatamab-in-patients

Safety and efficacy of elranatamab in patients with relapsed ... We treated 9 consecutive patients with advanced-stage AL amyloidosis with single-agent elranatamab, observing a 100% overall response and 67% ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40712156/

Safety and efficacy of elranatamab in patients with relapsed ... We treated 9 consecutive patients with advanced-stage AL amyloidosis with single-agent elranatamab, observing a 100% overall response and 67% ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06569147

NCT06569147 | Elranatamab in Patients with Relapsed or ... This study will evaluate the safety, tolerability and efficacy of elranatamab in patients with relapsed or refractory AL amyloidosis. Detailed Description. This ...

4. ash.confex.com ash.confex.com/ash/2024/webprogram/Paper200933.html

Elranatamab in Patients with Daratumumab Relapsed and/ ... There are no published data on Elranatamab in AL. Herein, we report safety and efficacy data on three consecutive, Daratumumab-refractory AL amyloidosis ...

5. imsannual2024.eventscribe.net imsannual2024.eventscribe.net/ajaxcalls/PosterInfo.asp?PosterID=692839

P-315: Safety and Efficacy of Elranatamab in Patients with ... There are currently no published data regarding the safety and efficacy of Elra in patients with AL amyloidosis. Methods: 3 adult pts with ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0006497125017707

Safety and efficacy of elranatamab in patients with ... No new adverse events were noted in patients with AL amyloidosis treated with elranatamab, including in patients with advanced heart failure.