Teclistamab vs Lenalidomide + Dexamethasone for Multiple Myeloma

Recruiting at2 trial locations

Overseen by Irene Ghobrial, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Irene Ghobrial, MD

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

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

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing a new drug called Teclistamab against a combination of two existing drugs, Lenalidomide and Dexamethasone, in people with high-risk smoldering multiple myeloma. The goal is to see which treatment is more effective in preventing the progression to active multiple myeloma. Teclistamab helps the immune system target cancer cells, while Lenalidomide and Dexamethasone work together to boost the immune response and reduce inflammation.

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.

What evidence supports the effectiveness of the drug combination of lenalidomide and dexamethasone for multiple myeloma?

Research shows that lenalidomide combined with dexamethasone is effective in treating multiple myeloma, improving survival and delaying disease progression compared to dexamethasone alone. This combination has been shown to work well even in patients who have tried other treatments before. ^{1 2 3 4 5}

What safety information is available for Lenalidomide and Dexamethasone in treating multiple myeloma?

Lenalidomide and Dexamethasone are generally safe for treating multiple myeloma, but common side effects include low blood cell counts, fatigue, muscle cramps, skin rash, infections, trouble sleeping, and blood clots. These side effects are manageable with proper care and monitoring. ^{3 6 7 8 9}

How is the drug Teclistamab different from Lenalidomide and Dexamethasone for treating multiple myeloma?

Teclistamab is a novel drug that works differently from Lenalidomide and Dexamethasone, as it is a bispecific antibody that targets both BCMA (B-cell maturation antigen) on myeloma cells and CD3 on T-cells, helping the immune system attack the cancer cells. This mechanism is distinct from Lenalidomide, which modulates the immune system and directly kills tumor cells, and Dexamethasone, a steroid that reduces inflammation and suppresses the immune response. ^{3 4 5 10 11}

Research Team

Irene Ghobrial, MD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Dexamethasone (Corticosteroid)
• Lenalidomide (Immunomodulatory Agent)
• Teclistamab (CAR T-cell Therapy)

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.

Participant Groups

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 Canada, Japan for the following indications:

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+

Giacomo Salvadore

Janssen Research & Development, LLC

Chief Medical Officer since 2023

MD from the University of Rome, Tor Vergata

Ricardo Attar

Janssen Research & Development, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology from the University of Buenos Aires

Findings from Research

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 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 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]

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]

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]

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 (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 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]

References

1. Japan 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. [2021]

2. England 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. [2018]

3. England pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Hematology: Lenalidomide plus dexamethasone is effective in multiple myeloma. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Lenalidomide: an update on evidence from clinical trials. [2018]

6. England 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. [2019]

7. England pubmed.ncbi.nlm.nih.gov

Treatment of plasma cell dyscrasias with lenalidomide. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Current treatment strategies with lenalidomide in multiple myeloma and future perspectives. [2018]

9. England pubmed.ncbi.nlm.nih.gov

United Kingdom myeloma forum position statement on the use of lenalidomide in multiple myeloma. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Lenalidomide in multiple myeloma. [2018]

11. New Zealand pubmed.ncbi.nlm.nih.gov

A review of lenalidomide in combination with dexamethasone for the treatment of multiple myeloma. [2021]