Tec-DR and Tal-DR for Multiple Myeloma

(MajesTEC-7 Trial)

Recruiting at 300 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Must not be taking: Corticosteroids

Disqualifiers: Stroke, Seizure, Allergies, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 196 days

1590 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing two new drug combinations to see if they work better than the current standard treatment for multiple myeloma. The new treatments aim to help the immune system find and destroy cancer cells more effectively.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you should not have received any prior therapy for multiple myeloma or smoldering myeloma, except for a short course of corticosteroids. It's best to discuss your current medications with the trial team.

What data supports the effectiveness of the drug combination Tec-DR and Tal-DR for treating multiple myeloma?

Research shows that combining daratumumab with lenalidomide and dexamethasone significantly improves outcomes for patients with multiple myeloma, including longer periods without disease progression and higher response rates. This suggests that similar combinations, like Tec-DR and Tal-DR, could also be effective. ^{1 2 3 4 5}

How is the Tec-DR and Tal-DR drug for multiple myeloma different from other treatments?

The Tec-DR and Tal-DR drug for multiple myeloma is unique because it combines daratumumab, a monoclonal antibody targeting CD38, with teclistamab, a bispecific antibody, which may offer a novel mechanism of action by engaging the immune system in a different way compared to standard treatments. This combination could potentially enhance the effectiveness of the treatment by targeting multiple pathways involved in the disease. ^{4 5 6 7 8}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for adults with newly diagnosed multiple myeloma who can't have high-dose chemotherapy with stem cell transplant due to age or other health issues. They should be able to perform daily activities (ECOG score 0-2) and must not plan on pregnancy or fathering children during the study.

Inclusion Criteria

I can take care of myself and am up and about more than half of my waking hours.

A participant must agree not to be pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of study treatment

I am newly diagnosed and not eligible for a specific intense treatment due to my age or health conditions.

Exclusion Criteria

I have only used a short course of steroids for my myeloma, not exceeding the specified dose.

You are allergic or have a bad reaction to the ingredients in teclistamab or talquetamab.

I am not allergic or unable to take daratumumab or lenalidomide.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Tec-DR or Tal-DR or DRd regimen, with cycles of 28 days each

Up to 196 days

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 9 years

Treatment Details

Interventions

• Daratumumab
• Dexamethasone
• Lenalidomide
• Teclistamab

Trial Overview The study compares two treatments: Teclistamab combined with Daratumumab and Lenalidomide (Tec-DR), versus Talquetamab with the same combination (Tal-DR). The goal is to see which treatment works better compared to a standard therapy of Daratumumab, Lenalidomide, and Dexamethasone.

Participant Groups

Group I: Teclistamab, Daratumumab SC, and Lenalidomide (Tec-DR) Experimental Treatment 3 Interventions

Participants will receive teclistamab as subcutaneous (SC) injection in combination with daratumumab and lenalidomide.

Group II: Talquetamab, Daratumumab SC, and Lenalidomide (Tal-DR) Experimental Treatment 3 Interventions

Participants will receive talquetamab as SC injection in combination with daratumumab and lenalidomide.

Group III: Daratumumab SC, Lenalidomide, and Dexamethasone (DRd) Active Control 3 Interventions

Participants will receive daratumumab as SC injection with lenalidomide and dexamethasone.

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

Approved in European Union as Darzalex for:

• Relapsed and refractory multiple myeloma
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone

Approved in United States as Darzalex for:

• Multiple myeloma in patients who have received at least three prior therapies
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone
• Relapsed or refractory multiple myeloma in combination with lenalidomide and dexamethasone

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

In the POLLUX study, after 25.4 months of follow-up, the combination of daratumumab with lenalidomide and dexamethasone significantly improved progression-free survival in patients with relapsed/refractory multiple myeloma, with a hazard ratio of 0.41 compared to lenalidomide/dexamethasone alone.

The overall response rate was notably higher with the daratumumab combination (92.9%) compared to the control (76.4%), and a significant proportion of patients achieved minimal residual disease negativity (26.2% vs 6.4%), indicating a deeper response without new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab plus lenalidomide and dexamethasone versus lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: updated analysis of POLLUX. Dimopoulos, MA., San-Miguel, J., Belch, A., et al.[2019]

Daratumumab, a monoclonal antibody targeting CD38, has shown significant anti-myeloma activity through various mechanisms, including direct apoptosis and immune system modulation, making it a key treatment for relapsed-refractory multiple myeloma (RRMM).

Clinical trials, such as CASTOR and POLLUX, demonstrated that daratumumab in combination with other therapies (like bortezomib and lenalidomide) significantly improves overall response rates and progression-free survival compared to standard treatments, leading to its approval and integration into clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab for the Management of Newly Diagnosed and Relapsed/Refractory Multiple Myeloma: Current and Emerging Treatments. Offidani, M., Corvatta, L., Morè, S., et al.[2021]

In a study of 162 multiple myeloma patients who received daratumumab, combining it with lenalidomide (DRd) showed no significant difference in progression-free survival (PFS) compared to combining it with pomalidomide (DPd) for those previously treated with lenalidomide.

Both treatment combinations (DRd and DPd) were found to be effective options for patients with relapsed/refractory multiple myeloma, indicating that daratumumab with lenalidomide remains a viable treatment strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab-lenalidomide and daratumumab-pomalidomide in relapsed lenalidomide-exposed or refractory multiple myeloma. Alhaj Moustafa, M., Parrondo, R., Abdulazeez, MF., et al.[2023]

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]

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 combined with lenalidomide and dexamethasone showed an impressive overall response rate of 81% in patients with relapsed/refractory multiple myeloma, indicating its efficacy in this challenging patient population.

The treatment was well tolerated, with no dose-limiting toxicities observed and manageable infusion-related reactions, suggesting a favorable safety profile consistent with previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma. Plesner, T., Arkenau, HT., Gimsing, P., et al.[2022]

Intravenous daratumumab, when combined with bortezomib, melphalan, and prednisone, significantly improves progression-free survival in patients with newly diagnosed multiple myeloma who cannot undergo autologous stem cell transplantation, as shown in the phase 3 ALCYONE trial.

The addition of daratumumab does not increase overall toxicity compared to the standard treatment, although it may lead to more infusion-related reactions and infections, making it a promising and relatively safe treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Combination Therapy for Transplant-Ineligible Newly Diagnosed Multiple Myeloma. Syed, YY.[2021]

In a study of 737 patients with newly diagnosed multiple myeloma, the addition of daratumumab to lenalidomide and dexamethasone significantly reduced the risk of disease progression or death, with a hazard ratio of 0.56, indicating a 44% lower risk compared to the control group.

Patients receiving daratumumab had a higher rate of complete response (47.6% vs. 24.9%) and a greater percentage achieving minimal residual disease status (24.2% vs. 7.3%), although they also experienced more severe side effects like neutropenia and pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. Facon, T., Kumar, S., Plesner, T., et al.[2023]

References

1. Italy pubmed.ncbi.nlm.nih.gov

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

2. Switzerland pubmed.ncbi.nlm.nih.gov

Daratumumab for the Management of Newly Diagnosed and Relapsed/Refractory Multiple Myeloma: Current and Emerging Treatments. [2021]

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

Daratumumab-lenalidomide and daratumumab-pomalidomide in relapsed lenalidomide-exposed or refractory multiple myeloma. [2023]

4. 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]

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

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

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

Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma. [2022]

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

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

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

Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. [2023]