Teclistamab + Daratumumab for Multiple Myeloma

(MajesTEC-3 Trial)

Not currently recruiting at 288 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must not be taking: Strong CYP3A4 inducers

Disqualifiers: Plasma cell leukemia, Waldenström's, POEMS, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 5 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new treatment options for people with multiple myeloma, a type of blood cancer. Researchers aim to assess the effectiveness of a new drug combination, including teclistamab (a type of immunotherapy) and daratumumab, compared to existing drug combinations. Participants will receive different treatments to determine which best slows or stops the disease. Eligible participants should have multiple myeloma with signs of disease progression after 1 to 3 prior treatments and should have used lenalidomide, a specific type of drug. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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, if you are taking a strong CYP3A4 inducer, you must stop it at least 5 half-lives before joining the trial.

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

Research has shown that the combination of teclistamab and daratumumab is generally well-tolerated by patients with multiple myeloma. While side effects occur, they are usually manageable. Common side effects include mild to moderate reactions like redness or swelling at the injection site and temporary low blood counts.

Research has found that combining daratumumab with pomalidomide and dexamethasone helps patients extend the time without disease progression. This combination is also generally safe, with common side effects like tiredness and low blood cell counts, often seen in cancer treatments.

Studies show that when daratumumab is used with bortezomib and dexamethasone, the combination is effective and has an acceptable safety profile. The side effects are similar to other treatments, including nausea and low platelet counts, which are important for blood clotting.

Overall, these treatments have been studied extensively and are considered safe enough for use in clinical settings, though they do come with some side effects. Prospective trial participants should consult their doctor to understand potential side effects and management strategies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about teclistamab-daratumumab (Tec-Dara) because it offers a novel approach for treating multiple myeloma. Unlike the standard treatments that primarily focus on targeting cancer cells with medications like bortezomib and lenalidomide, teclistamab is a bispecific antibody that engages T-cells to directly attack myeloma cells, potentially enhancing the immune response. Additionally, the combination of teclistamab with daratumumab, another antibody targeting CD38 on myeloma cells, may improve treatment efficacy through dual-targeting mechanisms. This innovative approach could lead to more effective treatments with the potential for improved patient outcomes.

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

Research has shown that combining teclistamab and daratumumab, which participants in this trial may receive in Arm A, may effectively treat multiple myeloma. Studies have found that this combination can significantly slow the disease, with 63% of patients responding well. In Arm B of this trial, participants may receive either the combination of daratumumab, pomalidomide, and dexamethasone (DPd), which has a higher response rate of 94%, with many patients experiencing a complete response, or the combination of daratumumab, bortezomib, and dexamethasone (DVd). The DVd combination has improved overall survival and reduced the risk of death by 26% compared to using only bortezomib and dexamethasone. These findings suggest that all these treatment combinations could be effective options for multiple myeloma. ^{2 6 7 8 9}

Who Is on the Research Team?

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Are You a Good Fit for This Trial?

This trial is for people with relapsed or refractory multiple myeloma who have tried 1-3 previous treatments including a proteasome inhibitor and lenalidomide. They should be relatively active (ECOG score of 0, 1, or 2), not allergic to the drugs used in the study, haven't had live vaccines recently, and haven't been treated with BCMA-directed therapy.

Inclusion Criteria

I have been diagnosed with multiple myeloma and it can be measured by tests.

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

My cancer has worsened after my last treatment, as confirmed by my doctor.

Exclusion Criteria

I have received treatment targeting BCMA before.

I have not had a live vaccine in the last 4 weeks.

I have taken a lot of steroids, like prednisone, recently.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Teclistamab and Daratumumab (Tec-Dara) or Daratumumab with Pomalidomide and Dexamethasone (DPd) or Daratumumab with Bortezomib and Dexamethasone (DVd)

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Bortezomib
• Daratumumab
• Dexamethasone
• Pomalidomide
• Teclistamab

Trial Overview The study tests Teclistamab combined with Daratumumab (Tec-Dara) against two other combinations: Daratumumab with Pomalidomide and Dexamethasone (DPd), or Daratumumab with Bortezomib and Dexamethasone (DVd). It aims to see which treatment works better for multiple myeloma that's come back or hasn't responded to past therapies.

How Is the Trial Designed?

Group I: Arm B: DPd or DVd Experimental Treatment 4 Interventions

Participants will be randomized either to daratumumab, pomalidomide, dexamethasone (DPd) treatment to receive daratumumab SC injection; pomalidomide orally; dexamethasone orally or intravenously, or to Daratumumab, Bortezomib, Dexamethasone (DVd) treatment to receive daratumumab SC injection; bortezomib SC injection, and dexamethasone orally or intravenously.

Group II: Arm A: Teclistamab-daratumumab (Tec-Dara) Experimental Treatment 2 Interventions

Participants will receive teclistamab and daratumumab by subcutaneous (SC) injection. Step-up doses of teclistamab will be given prior to the first full dose.

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

Approved in European Union as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in United States as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Canada as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Japan as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Who Is Running the Clinical Trial?

Janssen Research & Development, LLC

Lead 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

In a phase 3 trial involving 304 patients with relapsed or refractory multiple myeloma, the combination of daratumumab with pomalidomide and dexamethasone significantly improved progression-free survival compared to pomalidomide and dexamethasone alone, with a median of 12.4 months versus 6.9 months.

While the combination treatment was effective, it was associated with a higher incidence of grade 3 or 4 adverse events, particularly neutropenia, indicating that while daratumumab enhances treatment efficacy, it may also increase the risk of serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. Dimopoulos, MA., Terpos, E., Boccadoro, M., et al.[2021]

Daratumumab, a human CD38 monoclonal antibody, shows significant effectiveness in killing multiple myeloma cells that are resistant to lenalidomide and bortezomib, as demonstrated in both ex vivo assays and in vivo mouse models.

The combination of daratumumab with lenalidomide enhances the lysis of resistant myeloma cells and effectively reduces tumor growth in a xenograft model, suggesting a promising new treatment option for patients who do not respond to standard therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical Evidence for the Therapeutic Potential of CD38-Targeted Immuno-Chemotherapy in Multiple Myeloma Patients Refractory to Lenalidomide and Bortezomib. Nijhof, IS., Groen, RW., Noort, WA., et al.[2020]

Intravenous daratumumab, when combined with bortezomib, thalidomide, and dexamethasone, significantly improves treatment outcomes for adults with newly diagnosed multiple myeloma, leading to higher rates of stringent complete response and prolonged progression-free survival, as shown in the phase III CASSIOPEIA trial.

The addition of daratumumab has a minimal impact on overall toxicity, with the most common serious side effects being blood-related issues, indicating it is a relatively safe option for patients undergoing treatment for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma. Lamb, YN.[2021]

Daratumumab significantly improves overall survival (OS) compared to pomalidomide plus low-dose dexamethasone in patients with heavily pretreated multiple myeloma, with hazard ratios indicating a strong treatment benefit (0.56 and 0.51 for two different studies).

The survival advantage of daratumumab is even more pronounced in patients who have not previously been treated with pomalidomide, suggesting it may be particularly effective in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Efficacy of Daratumumab Monotherapy and Pomalidomide Plus Low-Dose Dexamethasone in the Treatment of Multiple Myeloma: A Matching Adjusted Indirect Comparison. Van Sanden, S., Ito, T., Diels, J., et al.[2019]

Daratumumab, when combined with lenalidomide and dexamethasone (DRd) or bortezomib and dexamethasone (DVd), showed an overall response rate of 80% in 171 heavily treated patients with relapsed/refractory multiple myeloma, indicating its efficacy in this challenging patient population.

Patients receiving the DRd combination experienced better progression-free survival (PFS) compared to those on DVd, with PFS rates of 84% and 77%, respectively, while the treatment was generally safe, with common side effects including neutropenia and infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab combined with dexamethasone and lenalidomide or bortezomib in relapsed/refractory multiple myeloma (RRMM) patients: Report from the multiple myeloma GIMEMA Lazio group. Fazio, F., Franceschini, L., Tomarchio, V., et al.[2022]

In a phase 3 study (CASTOR) with a median follow-up of 19.4 months, the combination of daratumumab, bortezomib, and dexamethasone significantly improved progression-free survival (16.7 months) compared to bortezomib and dexamethasone alone (7.1 months), indicating its efficacy in treating relapsed/refractory multiple myeloma.

Daratumumab plus bortezomib and dexamethasone also showed a higher overall response rate (83.8% vs. 63.2%) and was particularly beneficial for patients with one prior line of therapy, demonstrating a favorable safety profile consistent over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR. Spencer, A., Lentzsch, S., Weisel, K., et al.[2019]

Daratumumab, when combined with lenalidomide and dexamethasone or bortezomib and dexamethasone, significantly improves progression-free survival in patients with multiple myeloma who have received prior therapy, with reductions in the risk of disease progression or death by 63% and 61%, respectively.

The most common side effects reported were infusion reactions, diarrhea, and upper respiratory infections, with neutropenia and thrombocytopenia noted as important warnings, indicating that while daratumumab is effective, monitoring for these adverse reactions is essential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Daratumumab for Treatment of Multiple Myeloma After One Prior Therapy. Bhatnagar, V., Gormley, NJ., Luo, L., et al.[2022]

In a subgroup analysis of the CASTOR trial involving 498 patients, daratumumab combined with bortezomib and dexamethasone (D-Vd) significantly prolonged progression-free survival (PFS) in patients with high cytogenetic risk (12.6 months) compared to bortezomib and dexamethasone alone (6.2 months).

D-Vd also demonstrated a higher rate of minimal residual disease (MRD) negativity, indicating deeper responses in treatment effectiveness, while maintaining a safety profile consistent with the overall study population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk. Weisel, K., Spencer, A., Lentzsch, S., et al.[2021]

Daratumumab, a CD38-targeted monoclonal antibody, has been shown to be effective for treating relapsed multiple myeloma, particularly in patients who have undergone at least three prior therapies, including bortezomib and lenalidomide.

The drug has an excellent safety profile, with moderate-grade infusion-related reactions being the most common side effect, primarily occurring during the first infusion, highlighting its tolerability in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab for the treatment of multiple myeloma. Touzeau, C., Moreau, P.[2018]

Daratumumab is a monoclonal antibody that effectively targets CD38 on multiple myeloma cells, leading to cell death through various mechanisms such as complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity.

It has shown a favorable safety profile and significant clinical activity as both a standalone treatment and in combination with lenalidomide for patients with relapsed multiple myeloma who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. Xia, C., Ribeiro, M., Scott, S., et al.[2018]

Citations

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Efficacy and Safety of Daratumumab, Bortezomib ... Efficacy and safety of daratumumab, bortezomib, and dexamethasone (D-Vd) versus bortezomib and dexamethasone (Vd) in first relapse patients (pts) with multiple ...