Teclistamab vs Lenalidomide + Dexamethasone for Multiple Myeloma

Recruiting at 2 trial locations

Overseen By Ashlee Sturtevant, MSc

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Irene Ghobrial, MD

Must not be taking: Chemotherapy, Immunotherapy, Radiotherapy, others

Disqualifiers: Symptomatic multiple myeloma, Active infection, Uncontrolled illness, 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: 62

Duration: 24 months

52 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment, Teclistamab (a type of immunotherapy), against a standard combination of Lenalidomide and Dexamethasone to determine which more effectively slows the progression of high-risk smoldering multiple myeloma. Smoldering multiple myeloma involves abnormal plasma cells (a type of immune cell) that are present but not yet causing symptoms. The goal is to prevent the condition from developing into active multiple myeloma, a cancer that requires treatment. Suitable candidates for this trial have been diagnosed with high-risk smoldering multiple myeloma but do not yet show symptoms like bone pain or anemia (low red blood cells). As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that you cannot have had certain treatments like chemotherapy, immunotherapy, or radiotherapy recently. It's best to discuss your specific medications with the trial team.

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

Previous studies have identified some safety concerns with teclistamab. Many patients experienced infections, with about 67% being serious, indicating severe infections. Despite these issues, teclistamab has effectively treated multiple myeloma, suggesting that benefits might outweigh risks for some individuals.

In contrast, lenalidomide and dexamethasone are more established treatments. Lenalidomide, FDA-approved for multiple myeloma, is generally well-tolerated but can cause side effects like low blood counts and fatigue. Dexamethasone, a steroid, may lead to mood changes and high blood sugar. The combination of these drugs has been used in treating multiple myeloma for some time, providing a well-known safety profile.

Prospective participants should weigh these factors and discuss them with their doctor when considering joining a study. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Teclistamab for multiple myeloma because it offers a novel approach compared to traditional therapies like Lenalidomide and Dexamethasone. Unlike these standard treatments, which generally modulate the immune system and inhibit cancer cell growth, Teclistamab is a bispecific antibody that specifically targets BCMA (B-cell maturation antigen) on myeloma cells. This unique mechanism allows it to directly engage and activate T-cells to attack the cancer cells more precisely. By potentially offering a more targeted attack on the disease, Teclistamab could lead to improved outcomes for patients with multiple myeloma.

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

Research has shown that Teclistamab, one of the treatments tested in this trial, yields promising results for treating multiple myeloma. In studies with patients whose multiple myeloma returned after treatment or did not respond to treatment, Teclistamab shrank or eliminated cancer in up to 63% of cases. Many patients experienced a reduction or disappearance of their cancer. Meanwhile, Lenalidomide combined with Dexamethasone, the other treatment option in this trial, is a well-known regimen that helps the immune system slow or stop cancer growth. Both treatments show potential for treating high-risk smoldering multiple myeloma, which can develop into active cancer. ^{2 6 7 8 9}

Who Is on the Research Team?

Irene Ghobrial, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults over 18 with high-risk smoldering multiple myeloma, which is a pre-cancerous stage of plasma cell cancer without symptoms. Participants must have certain blood and bone marrow conditions, be able to perform daily activities (ECOG 0-2), and not have had previous SMM treatments in the last 6 months. Women who can bear children must follow strict pregnancy prevention measures.

Inclusion Criteria

You have a high amount of a type of cells called BMPC in your bone marrow.

Your test results must be within the normal range for certain lab values.

You have a high risk of developing multiple myeloma based on specific criteria or a total score of 9.

Exclusion Criteria

Pregnant, breast-feeding, or planning pregnancy within the study period

I have not had myelodysplastic syndrome or any cancer in the last 2 years.

You have a confirmed active viral infection with certain specified viruses.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Initial safety assessment of Teclistamab with up to 6 participants to establish safety before proceeding to full randomization

4 weeks

Frequent monitoring during the first 28 days

Treatment

Participants receive either Teclistamab or Lenalidomide + Dexamethasone combination for up to 24 months

24 months

Monthly visits for each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Dexamethasone
• Lenalidomide
• Teclistamab

Trial Overview The study tests Teclistamab's effectiveness against a combination of Lenalidomide and Dexamethasone in patients with high-risk smoldering multiple myeloma. It aims to find out if early treatment can prevent progression to active multiple myeloma.

How Is the Trial Designed?

Group I: Teclistamab Experimental Treatment 1 Intervention

Each study treatment cycle lasts 28 days. Participants will be randomized into either Teclistamab arm or Lenalidomine + Dexamethoasone arm \- Teclistamab-Per Protocol

Group II: Lenalidomide + Dexamethasone (LD) Active Control 2 Interventions

Each study treatment cycle lasts 28 days. Participants will be randomized into either Teclistamab arm or Lenalidomine + Dexamethoasone arm * Lenalidomine * Dexamethoasone

Dexamethasone is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases
• Immune system disorders

Approved in United States as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders
• Neoplastic diseases
• Nervous system disorders

Approved in Canada as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases

Approved in Japan as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders

Who Is Running the Clinical Trial?

Irene Ghobrial, MD

Lead Sponsor

Trials

1

Recruited

50+

Janssen Research & Development, LLC

Industry Sponsor

Trials

1,022

Recruited

6,408,000+

Joaquin Duato

Janssen Research & Development, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Research & Development, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

A subgroup analysis from two phase III clinical trials demonstrated that combining lenalidomide with dexamethasone is more effective than using dexamethasone alone for patients with relapsed or refractory multiple myeloma who had prior treatment with thalidomide.

This finding suggests that the lenalidomide and dexamethasone combination could be a more beneficial treatment option for these patients, potentially improving their outcomes in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hematology: Lenalidomide plus dexamethasone is effective in multiple myeloma. Meijer, E., Sonneveld, P.[2021]

Lenalidomide is a powerful treatment for multiple myeloma (MM) that works by directly causing cancer cell death, preventing cancer cells from sticking to bone marrow, and enhancing the body's immune response against tumors.

In combination with dexamethasone, lenalidomide has shown superior effectiveness in clinical trials, leading to improved patient outcomes such as longer survival and FDA approval for treating relapsed MM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of lenalidomide in combination with dexamethasone for the treatment of multiple myeloma. Hideshima, T., Raje, N., Richardson, PG., et al.[2021]

Lenalidomide is a more potent and less toxic alternative to thalidomide, showing significant efficacy in treating relapsed or refractory multiple myeloma, both as a single agent and in combination with other treatments.

While lenalidomide leads to high response rates and improved survival in multiple myeloma patients, it carries a risk of thromboembolism, particularly when used with steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of plasma cell dyscrasias with lenalidomide. Dimopoulos, MA., Kastritis, E., Rajkumar, SV.[2018]

Lenalidomide, when combined with dexamethasone, significantly improves response rates and survival in patients with relapsed/refractory multiple myeloma, showing a response rate of 60% compared to 20% with placebo in Phase III trials.

While lenalidomide is effective, it is associated with common adverse events such as hematologic toxicity and venous thromboembolism, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current treatment strategies with lenalidomide in multiple myeloma and future perspectives. Larocca, A., Cavallo, F., Mina, R., et al.[2018]

In a pooled analysis of two phase III trials involving 704 patients with relapsed or refractory multiple myeloma, lenalidomide combined with dexamethasone significantly improved the overall response rate compared to placebo plus dexamethasone across all age groups.

Lenalidomide plus dexamethasone also prolonged progression-free survival and time-to-progression in all age groups, indicating its efficacy as a treatment option for multiple myeloma, although the overall survival benefit was not statistically significant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone improves survival and time-to-progression in patients ≥65 years old with relapsed or refractory multiple myeloma. Chanan-Khan, AA., Lonial, S., Weber, D., et al.[2021]

In a phase 3 trial involving 301 transplant-ineligible patients with newly diagnosed multiple myeloma, the combination of pembrolizumab with lenalidomide and dexamethasone did not show a significant improvement in progression-free survival compared to lenalidomide and dexamethasone alone, with 6-month estimates of 82.0% vs 85.0%.

The addition of pembrolizumab was associated with a higher rate of serious adverse events (54% vs 39%) and treatment-related deaths (4% vs 1%), leading to an unfavorable benefit-risk profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus lenalidomide and dexamethasone for patients with treatment-naive multiple myeloma (KEYNOTE-185): a randomised, open-label, phase 3 trial. Usmani, SZ., Schjesvold, F., Oriol, A., et al.[2019]

In a study involving 98 relapsed refractory multiple myeloma patients, treatment with lenalidomide plus dexamethasone resulted in a 52% overall response rate, with 49% achieving partial remission and 3% achieving complete remission, despite patients having undergone a median of 5 prior treatments.

The combination therapy not only provided rapid responses but also extended overall survival by nearly six months, demonstrating its efficacy and safety regardless of previous treatments with thalidomide and bortezomib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in relapsed refractory myeloma patients: impact of previous response to bortezomib and thalidomide on treatment efficacy. Results of a medical need program in Belgium. Delforge, M., Michiels, A., Doyen, C., et al.[2018]

Lenalidomide (Revlimid) has been rapidly developed and recently approved for treating relapsed multiple myeloma, showing durable clinical responses, especially when combined with dexamethasone.

Clinical trials indicate that lenalidomide is generally well tolerated by patients, with manageable side effects, making it a promising option for those with relapsed and refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in multiple myeloma. Richardson, PG., Mitsiades, C., Hideshima, T., et al.[2018]

Lenalidomide, when combined with dexamethasone, has shown superior efficacy in treating relapsed multiple myeloma compared to dexamethasone alone, as demonstrated in two large phase III studies that reported improved response rates, progression-free survival, and overall survival.

The drug is administered orally in a 21-day cycle and has manageable side effects, such as neutropenia and venous thrombotic events, making it a viable treatment option for patients who have undergone at least one prior therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

United Kingdom myeloma forum position statement on the use of lenalidomide in multiple myeloma. Davies, F., Morris, C., Bird, J., et al.[2018]

Lenalidomide combined with dexamethasone has been shown to be effective for treating relapsed/refractory multiple myeloma, and it has received approval from both the FDA and EMA for patients who have undergone at least one prior therapy.

The most common serious side effects include cytopenias and infections, but an expert panel has provided management strategies to minimize these risks, ensuring that patients can receive the full benefits of the treatment without unnecessary dose reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma. Palumbo, A., Dimopoulos, M., San Miguel, J., et al.[2018]

Lenalidomide, when combined with dexamethasone, significantly improves clinical response rates, progression-free survival (PFS), and overall survival (OS) in patients with relapsed/refractory multiple myeloma compared to dexamethasone alone, as shown in Phase III clinical trials.

The treatment is generally well tolerated, with manageable side effects like myelosuppression and venous thromboembolic complications, and it can be effectively used in patients with renal impairment with appropriate dose adjustments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: an update on evidence from clinical trials. Dimopoulos, MA., Terpos, E.[2018]

Citations

1. nature.com nature.com/articles/s41408-025-01314-9

Outcomes of teclistamab in patients with relapsed/ ... Treatment with SOC teclistamab yielded an ORR of 48.7% in the prior BCMA-DT group, which compares favorably with the ORR of 52.5% reported in ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40352937/

Effectiveness and safety of teclistamab for relapsed or ... Teclistamab continues to be a promising and effective treatment option for RRMM patients, including those previously exposed to BCMA-targeted therapies.

3. ashpublications.org ashpublications.org/bloodadvances/article/9/19/4806/546235/The-efficacy-of-teclistamab-in-patients-with

The efficacy of teclistamab in patients with multiple myeloma ... Long-term follow-up results of the MajesTec trial have shown promising efficacy of teclistamab in RRMM with overall response rate (ORR) of 63% ...

4. aacr.org aacr.org/about-the-aacr/newsroom/news-releases/real-world-data-shows-teclistamab-can-benefit-many-multiple-myeloma-patients-who-would-have-been-ineligible-for-pivotal-trial/

Real-world Data Shows Teclistamab Can Benefit Many ... PHILADELPHIA – Teclistamab-cqyv (Tecvayli) led to clinically meaningful responses in patients with heavily pretreated multiple myeloma who ...

5. tecvaylihcp.com tecvaylihcp.com/clinical-study-results/

Clinical Study Results | TECVAYLI® (teclistamab-cqyv) HCP The efficacy of TECVAYLI® was evaluated in 110 patients with relapsed or refractory multiple myeloma in the single-arm, open-label, multi-center, phase 1/2 ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39090994

Safety outcomes of teclistamab accelerated dose escalation This article examines safety event rates following the implementation of a 2-day separation between step-up doses at one institution to streamline patient care.

7. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/2398/532408/Dosing-Patterns-and-Early-Safety-and-Effectiveness

Dosing Patterns and Early Safety and Effectiveness Outcomes ... Dosing patterns and early safety and effectiveness outcomes in patients with multiple myeloma treated with Teclistamab in the community setting.

8. nejm.org nejm.org/doi/full/10.1056/NEJMoa2203478

Teclistamab in Relapsed or Refractory Multiple Myeloma Teclistamab resulted in a high rate of deep and durable response in patients with triple-class–exposed relapsed or refractory multiple myeloma.

9. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.e19504

Real-world outcomes of teclistamab for the treatment ... The incidence of infection was 67%; the majority were grade ≥ 3. The overall response rate (ORR) by IMWG criteria was 50%. All patients who ...