Elranatamab vs Daratumumab for Multiple Myeloma

(ELDORADO Trial)

Not yet recruiting at 2 trial locations

Overseen By Andrew Yee, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Massachusetts General Hospital

Must be taking: Thromboembolism prophylaxis

Disqualifiers: HIV, Hepatitis B, Hepatitis C, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 3

Duration: 24 cycles (each cycle is 28 days)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two different treatment combinations to determine which is more effective for people with newly diagnosed multiple myeloma, a type of blood cancer. One group receives a mix of elranatamab (an experimental treatment), lenalidomide, bortezomib, and dexamethasone, while the other group receives daratumumab, lenalidomide, bortezomib, and dexamethasone. The goal is to compare the effectiveness and safety of these treatments. This trial may suit those diagnosed with multiple myeloma who are not eligible for or have postponed stem cell transplant options. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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 your specific medications with the study team to get a clear answer.

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

In previous studies, elranatamab has demonstrated a safety profile that patients with multiple myeloma can manage. Research indicates it is well-tolerated, even in those with high-risk conditions. Some patients have achieved minimal residual disease negativity, a positive outcome. However, the FDA has not yet approved the combination of elranatamab with other drugs in the trial.

For daratumumab, studies have shown it is generally well-tolerated in myeloma treatments. Over several years of follow-up, no new safety concerns have been reported. Daratumumab is already approved for use with standard myeloma treatments, suggesting it is relatively safe.

Both treatments have been tested in various settings, showing acceptable safety profiles. However, individual experiences with side effects can vary. Always discuss potential risks and benefits with the trial team. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Elranatamab for multiple myeloma because it offers a novel approach by targeting the BCMA (B-cell maturation antigen), which is different from most standard treatments like Daratumumab that target CD38. Elranatamab's unique mechanism of action might provide a new pathway for attacking multiple myeloma cells, potentially leading to better outcomes. Additionally, Elranatamab is administered via subcutaneous injection, which could offer more convenience and comfort compared to some existing intravenous therapies.

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

Research has shown that both elranatamab and daratumumab are promising treatments for multiple myeloma, a type of blood cancer. In this trial, participants will be randomized to receive either elranatamab with lenalidomide, bortezomib, and dexamethasone (elra-RVd lite) or daratumumab with lenalidomide, bortezomib, and dexamethasone (dara-RVd lite). Studies have demonstrated that elranatamab led to improvement in all patients with advanced disease. Similarly, when combined with lenalidomide and bortezomib, daratumumab proved very effective, with over 90% of patients responding well in some studies. These treatments target and destroy cancer cells, offering hope for those with multiple myeloma. ^{1 6 7 8 9}

Who Is on the Research Team?

Andrew Yee, MD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

This trial is for newly diagnosed multiple myeloma patients who are not eligible or have deferred a transplant. Specific eligibility criteria details were not provided, so interested individuals should contact the study organizers for more information.

Inclusion Criteria

I am 18 years old or older.

I have been newly diagnosed with multiple myeloma and meet specific health criteria.

My cancer can be measured by tests.

Exclusion Criteria

I have moderate to severe numbness, tingling, or pain in my hands or feet.

I have a history of serious heart, brain, hormone, stomach, lung, or inflammation diseases.

I have not received a live vaccine in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

The first 10 patients will enroll in the elranatamab arm for a one 14-day safety run-in cycle

2 weeks

3 visits (in-person)

Treatment

Patients receive treatment for 24 cycles with elranatamab or daratumumab in combination with lenalidomide, bortezomib, and dexamethasone

24 cycles (each cycle is 28 days)

Multiple visits per cycle (in-person and virtual)

Observation

Patients who have had two MRD negative tests, one year apart, may discontinue treatment and enter the observation phase

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Primarily through chart review

What Are the Treatments Tested in This Trial?

Interventions

• Daratumumab
• Elranatamab

Trial Overview The trial compares two drug combinations: Elranatamab with lenalidomide, bortezomib, and dexamethasone versus Daratumumab with the same additional drugs in treating new multiple myeloma cases.

How Is the Trial Designed?

Group I: Elranatamab with lenalidomide, bortezomib, and dexamethasone (elra-RVd lite) Experimental Treatment 4 Interventions

The first 10 patients will enroll in the elranatamab arm for a one 14-day safety run-in cycle. Elranatamab and dexamethasone will be administered at pre-determined doses on days 1, 4, and 8 of the cycle. After randomization occurs, patients in the elra-RVd lite arm will complete 24 cycles (each cycle is 28 days) of treatment. On day 1 of each cycle and day 15 of cycle 1, the pre-determined dose of elranatamab will be administered via subcutaneous injection. On days 1-21 of each cycle, patients will take the pre-determined dose of oral lenalidomide. One days 1, 8, and 15 of cycles 1-8, the pre-determined dose of bortezomib will be administered via subcutaneous injection. After completion of 24 treatment cycles, patients who have had two MRD negative tests, one year apart, may discontinue treatment and enter the observation phase of the trial. Patients who have not had two MRD negative tests one year apart, may continue elranatamab lenalidomide treatment for another 24 cycles.

Group II: Daratumumab with lenalidomide, bortezomib, and dexamethasone (dara-RVd lite) Experimental Treatment 4 Interventions

After randomization occurs, patients in the dara-RVd lite arm will complete 24 cycles (each cycle is 28 days) of treatment. On days 1, 8, 15, and 22 of cycles 1 and 2, days 1 and 15 of cycles 3-6, and day 1 of cycles 7+, the pre-determined dose of daratumumab will be administered via subcutaneous injection. On days 1-21 of each cycle, patients will take the pre-determined dose of oral lenalidomide. One days 1, 8, and 15 of cycles 1-8, the pre-determined dose of bortezomib will be administered via subcutaneous injection. On days 1, 2, 8, 9, 15, 16 of cycles 3+, as well as days 22 and 23 of cycles 1 and 2, patients will take the pre-determined dose of oral dexamethasone.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

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

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2312054

Daratumumab, Bortezomib, Lenalidomide, and ... An evaluation of subcutaneous daratumumab combined with bortezomib, lenalidomide, and dexamethasone (VRd) for the treatment of transplantation-eligible patients

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12025356/

Real-World Data on the Efficacy of Daratumumab in ... In the Pollux and Castor studies, the efficacy of daratumumab was demonstrated, with overall response rates (ORRs) of 92.9% and 82.9% and a ...

3. ashpublications.org ashpublications.org/bloodadvances/article/9/13/3129/536049/Early-daratumumab-therapy-improves-renal-outcomes

Early daratumumab therapy improves renal outcomes in ... Early use of daratumumab combinations in patients with MM admitted with kidney injury rapidly reduces sFLCs. Early initiation of daratumumab ...

4. tandfonline.com tandfonline.com/doi/full/10.1080/16078454.2024.2399430

Efficacy of daratumumab on multiple myeloma patients with ... Our results indicate that MM patients with RI could benefit from a daratumumab-added regimen regardless of MM status.

5. sciencedirect.com sciencedirect.com/science/article/pii/S0959804924017647

Characteristics and outcomes in patients with lenalidomide ... Newer drugs for multiple myeloma (MM) have improved patient outcomes; however, nearly all patients will relapse and require subsequent therapy [1], [2].

6. ashpublications.org ashpublications.org/blood/article/145/15/1658/534407/Efficacy-and-safety-of-daratumumab-in-intermediate

Efficacy and safety of daratumumab in intermediate/high-risk ... No new safety concerns were observed after extended follow-up of ∼7 years, highlighting the tolerability of daratumumab. Subjects: Clinical Trials and ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10850248/

Daratumumab-based immunotherapy vs. lenalidomide ... Meta-analysis results showed that The daratumumab-based regimen showed a significantly higher CR/sCR rate than RVD/RVD-lite for TIE-NDMM (47% vs. 24%, P<0.01).

8. clinicaltrials.gov clinicaltrials.gov/study/NCT06348147

NCT06348147 | Dara-RVd Induction for Newly Diagnosed ... This Phase II hybrid decentralized trial will examine the effect of daratumumab-based quadruplet induction therapy administered at an attenuated schedule in ...

9. darzalexhcp.com darzalexhcp.com/multiple-myeloma-resources/

Multiple Myeloma Resources - darzalex faspro Select Important Safety Information. ... DARZALEX® is contraindicated in patients with a history of severe hypersensitivity, for example, anaphylactic reactions, ...