Teclistamab + Lenalidomide for Multiple Myeloma

(MajesTEC-4 Trial)

Recruiting at 250 trial locations

Overseen By Sabrin Tahri

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Stichting European Myeloma Network

Must not be taking: BCMA-directed, Immune cell redirecting

Disqualifiers: Prior BCMA therapy, Gene therapy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

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

Compensation: Varies

Number of Visits: Unknown

Duration: up to 8 years

1594 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a multicenter, randomized, open-label, Phase 3 study in participants with newly diagnosed multiple myeloma to evaluate the benefits of teclistamab in combination with lenalidomide and teclistamab alone versus lenalidomide alone as maintenance therapy after autologous stem cell transplant.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you must not have received any maintenance therapy before joining the trial.

What data supports the effectiveness of the drug combination Teclistamab and Lenalidomide for treating multiple myeloma?

Lenalidomide, when used in combination with other drugs like dexamethasone, has shown to be effective in treating multiple myeloma, especially in patients who have relapsed or have not responded to previous treatments. It has been associated with improved survival and quality of life in patients with newly diagnosed multiple myeloma who are not eligible for stem-cell transplantation. ^{1 2 3 4 5}

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

Lenalidomide, used for multiple myeloma, can cause side effects like fatigue, skin rash, low blood cell counts (neutropenia and thrombocytopenia), and blood clots (venous thromboembolism). Careful monitoring and managing these side effects are important to ensure safe treatment. ^{3 6 7 8 9}

What makes the drug combination of Teclistamab and Lenalidomide unique for treating multiple myeloma?

The combination of Teclistamab and Lenalidomide is unique because it pairs an immunomodulatory drug (Lenalidomide) with a novel agent (Teclistamab) that may offer a new mechanism to overcome resistance and maintain remission in multiple myeloma, potentially providing a more effective treatment option compared to existing therapies. ^{1 2 5 10 11}

Research Team

Niels van de Donk, Professor

Principal Investigator

Amsterdam UMC, Vrije Universiteit Amsterdam

Elena Zamagni, Professor

Principal Investigator

IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia "Seràgnoli"

Eligibility Criteria

This trial is for individuals newly diagnosed with multiple myeloma who have had only one line of therapy and achieved at least a partial response. They must not have received maintenance therapy, should be relatively fit (ECOG score 0-2), and their lab values need to be within certain limits. People intolerant to lenalidomide or those who've had previous maintenance treatments can't participate.

Inclusion Criteria

Have clinical laboratory values within prespecified range.

I have not received any maintenance therapy.

I can care for myself and am up and about more than 50% of my waking hours.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive maintenance therapy with teclistamab in combination with lenalidomide, teclistamab alone, or lenalidomide alone following autologous stem cell transplantation

up to 8 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Lenalidomide
• Teclistamab

Trial Overview The study compares the effectiveness of teclistamab combined with lenalidomide and teclistamab alone against just lenalidomide as post-autologous stem cell transplant maintenance therapy in new multiple myeloma patients. It's a Phase 3 trial where participants are randomly assigned to these treatment groups.

Participant Groups

Group I: Arm C Teclistamab-Alone (Tec) Experimental Treatment 1 Intervention

Teclistamab will be administered via a subcutaneous injection (SC)

Group II: Arm A: Teclistamab-Lenalidomide (Tec-Len) Experimental Treatment 2 Interventions

Teclistamab will be administered via a subcutaneous injection (SC)

Group III: Arm B Lenalidomide Alone (Len) Active Control 1 Intervention

Lenalidomide orally.

Lenalidomide is already approved in European Union, United States for the following indications:

Approved in European Union as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Approved in United States as Revlimid for:

• Multiple myeloma
• Myelodysplastic syndromes
• Mantle cell lymphoma
• Follicular lymphoma
• Marginal zone lymphoma

Who Is Running the Clinical Trial?

Stichting European Myeloma Network

Lead Sponsor

Trials

28

Recruited

18,600+

European Myeloma Network

Lead Sponsor

Trials

27

Recruited

12,600+

Janssen Pharmaceutica

Industry Sponsor

Trials

43

Recruited

9,200+

Founded

1953

Headquarters

Beerse, Belgium

Known For

Immunology Treatments

Top Products

Stelara (ustekinumab), Darzalex (daratumumab), Remicade (infliximab), Tremfya (guselkumab)

Findings from Research

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]

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, a derivative of thalidomide, has improved potency and a better side-effect profile, particularly with reduced neurologic toxicity compared to its predecessor.

While lenalidomide shows promise in treating conditions like myelodysplastic syndrome and multiple myeloma, there are still concerns about pro-thrombotic effects, especially when used with dexamethasone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: an immunomodulatory drug. Crane, E., List, A.[2018]

Lenalidomide significantly improves progression-free survival (PFS) in patients with newly diagnosed multiple myeloma not eligible for stem-cell transplantation, as shown in randomized trials like the FIRST and MM-015 trials.

Continuous lenalidomide therapy is associated with less toxicity compared to thalidomide, maintaining tolerability without increasing the risk of neutropenia or second primary malignancies, making it a safer long-term treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: a review of its continuous use in patients with newly diagnosed multiple myeloma not eligible for stem-cell transplantation. McCormack, PL.[2018]

Immunomodulatory drugs like thalidomide and lenalidomide have shown significant effectiveness in treating multiple myeloma and related blood disorders, demonstrating high response rates across various treatment phases.

These drugs not only target cancer cells directly but also enhance the immune response within the bone marrow, and have been successfully combined with other treatments, leading to FDA approval for their use in multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic use of immunomodulatory drugs in the treatment of multiple myeloma. Raje, N., Hideshima, T., Anderson, KC.[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 has shown significant efficacy in improving survival rates for patients with relapsed and refractory myeloma, especially when used alongside other treatments like bortezomib and thalidomide.

While lenalidomide is effective, it is associated with common side effects such as fatigue and thrombocytopenia, and its combination with other agents can increase the risk of blood clots, highlighting the importance of managing these adverse events for continued treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide for the treatment of relapsed and refractory multiple myeloma. van de Donk, NW., Görgün, G., Groen, RW., et al.[2021]

Lenalidomide is an effective treatment for patients with relapsed or refractory multiple myeloma, showing promising clinical activity and is approved by the FDA.

Common side effects of lenalidomide include neutropenia, thrombocytopenia, and thromboembolic events, necessitating careful monitoring to prevent serious complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: a new agent for patients with relapsed or refractory multiple myeloma. Tariman, JD.[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, when combined with dexamethasone, significantly improves time to progression in patients with multiple myeloma compared to placebo, as shown in two randomized, double-blind studies.

However, the treatment is associated with serious side effects, including increased risks of neutropenia, thrombocytopenia, and thromboembolic events, leading to its restricted distribution under the RevAssist program.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of multiple myeloma after one prior therapy. Hazarika, M., Rock, E., Williams, G., et al.[2020]

Lenalidomide has become a crucial treatment option for multiple myeloma and del-5q myelodysplastic syndromes, and it has been tested for various other cancers, showcasing its broad therapeutic potential.

The drug received FDA approval for use in combination with dexamethasone for previously treated multiple myeloma, highlighting its efficacy and safety in this specific patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide: a novel anticancer drug with multiple modalities. Galustian, C., Dalgleish, A.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Lenalidomide in multiple myeloma. [2018]

2. England pubmed.ncbi.nlm.nih.gov

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

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

Lenalidomide: an immunomodulatory drug. [2018]

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

Lenalidomide: a review of its continuous use in patients with newly diagnosed multiple myeloma not eligible for stem-cell transplantation. [2018]

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

Therapeutic use of immunomodulatory drugs in the treatment of multiple myeloma. [2018]

6. England pubmed.ncbi.nlm.nih.gov

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

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

Lenalidomide for the treatment of relapsed and refractory multiple myeloma. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Lenalidomide: a new agent for patients with relapsed or refractory multiple myeloma. [2018]

9. 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]

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

Lenalidomide in combination with dexamethasone for the treatment of multiple myeloma after one prior therapy. [2020]

11. England pubmed.ncbi.nlm.nih.gov

Lenalidomide: a novel anticancer drug with multiple modalities. [2019]