Teclistamab + Daratumumab for Multiple Myeloma

(MajesTEC-3 Trial)

Recruiting at 246 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

587 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a new antibody treatment combined with daratumumab for patients whose multiple myeloma has returned and does not respond to standard treatments. The treatment helps the immune system recognize and attack cancer cells by targeting a specific protein. Daratumumab, approved in 2015, is a monoclonal antibody targeting CD38 on multiple myeloma cells.

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.

What data supports the effectiveness of the drug combination Teclistamab + Daratumumab for Multiple Myeloma?

Research shows that daratumumab, when combined with other drugs like bortezomib and dexamethasone, significantly improves patient outcomes in multiple myeloma by increasing the rate of complete responses and prolonging the time patients live without the disease getting worse. This suggests that combining daratumumab with other treatments could be effective for multiple myeloma. ^{1 2 3 4 5}

Is the combination of Teclistamab and Daratumumab safe for treating multiple myeloma?

Daratumumab, when combined with other drugs like bortezomib and dexamethasone, has been shown to be generally safe for treating multiple myeloma, with common side effects including infusion reactions, diarrhea, and infections. Serious blood-related side effects like neutropenia (low white blood cell count) and thrombocytopenia (low platelet count) have been noted, but overall, it has an excellent safety profile. ^{1 4 6 7 8}

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

The combination of Teclistamab and Daratumumab for multiple myeloma is unique because it includes Teclistamab, a novel bispecific antibody that targets both BCMA (B-cell maturation antigen) and CD3, potentially enhancing the immune system's ability to attack cancer cells. This combination, along with other drugs like Bortezomib and Pomalidomide, offers a new approach for patients who may not respond to standard treatments. ^{1 3 9 10 11}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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

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]

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]

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 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]

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, 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 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 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]

References

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

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

2. England 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. [2021]

3. United States 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. [2020]

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

Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk. [2021]

5. England 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. [2019]

6. United States 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. [2022]

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

Daratumumab for the treatment of multiple myeloma. [2018]

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

FDA Approval Summary: Daratumumab for Treatment of Multiple Myeloma After One Prior Therapy. [2022]

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

Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. [2023]

10. Italy pubmed.ncbi.nlm.nih.gov

Daratumumab plus bortezomib and dexamethasone versus bortezomib and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of CASTOR. [2019]

11. Spain pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. [2018]