Teclistamab Combination Therapy for Multiple Myeloma

(MajesTEC-2 Trial)

Recruiting at 33 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Janssen Research & Development, LLC

Must not be taking: Corticosteroids, Live vaccines

Disqualifiers: HIV, CNS involvement, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years and 5 months

140 Participants Needed

Trial Summary

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 should not have received certain treatments recently, like live vaccines or high doses of corticosteroids, before starting the study.

What data supports the effectiveness of the drug teclistamab for multiple myeloma?

Teclistamab has shown effectiveness in treating multiple myeloma, with a pivotal trial demonstrating an overall response rate of more than 60% in heavily pretreated patients. It is approved by the FDA and EMA for patients who have received multiple prior therapies, indicating its potential as a treatment option for relapsed or refractory multiple myeloma. ^{1 2 3 4 5}

Is teclistamab combination therapy safe for humans?

Teclistamab, used for treating multiple myeloma, has shown some side effects like cytokine release syndrome (a condition where the immune system releases too many proteins into the blood too quickly), infections, and neurotoxicity (damage to the nervous system). However, it is considered more tolerable for elderly patients compared to other similar treatments. ^{1 2 4 5 6}

What makes the drug Teclistamab unique for treating multiple myeloma?

Teclistamab is unique because it is a bispecific antibody, which means it can bind to two different targets at once, specifically targeting and engaging the immune system to attack multiple myeloma cells. This approach is different from traditional treatments that often target a single pathway or mechanism. ^{7 8 9 10 11}

What is the purpose of this trial?

This trial tests the safety and tolerability of teclistamab when used with other treatments. It aims to find the best dose and ensure it is safe for patients. Teclistamab has shown promising results in treating a specific type of cancer.

Research Team

Janssen Research and Development, LLC Clinical Trial

Principal Investigator

Janssen Research and Development LLC

Eligibility Criteria

This trial is for adults with multiple myeloma who have measurable disease and meet specific treatment requirements. Women of childbearing potential must test negative for pregnancy and agree to ongoing tests. Participants cannot have had prior BCMA-targeted therapy (except for one regimen), recent live vaccines, high steroid doses, or active brain involvement of cancer.

Inclusion Criteria

You have a specific type of disease that can be measured by certain standards at the screening.

My multiple myeloma diagnosis follows international guidelines.

Meet treatment regimen-specific requirements as specified for each treatment regimen

Exclusion Criteria

You have tested positive for HIV.

I have or might have myeloma affecting my brain or spinal cord.

I have not received a live vaccine in the last 30 days.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive teclistamab in combination with other anticancer therapies in various regimens

Up to 2 years and 5 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Bortezomib
• Daratumumab
• Lenalidomide
• Nirogacestat
• Pomalidomide
• Teclistamab

Trial Overview The study is testing the safety and best dose of Teclistamab in combination with other anticancer drugs like Daratumumab, Pomalidomide, Lenalidomide, Bortezomib, and Nirogacestat in treating multiple myeloma.

Participant Groups

Group I: Treatment Regimen F: Teclistamab + Daratumumab + Lenalidomide + Bortezomib (28-day Cycles) Experimental Treatment 4 Interventions

Participants will receive teclistamab plus daratumumab plus lenalidomide plus bortezomib in 28-day cycles.

Group II: Treatment Regimen E: Teclistamab + Daratumumab + Lenalidomide Experimental Treatment 3 Interventions

Participants will receive teclistamab plus daratumumab plus lenalidomide.

Group III: Treatment Regimen D: Teclistamab + Lenalidomide Experimental Treatment 2 Interventions

Participants will receive teclistamab plus lenalidomide.

Group IV: Treatment Regimen C: Teclistamab + Nirogacestat Experimental Treatment 2 Interventions

Participants will receive teclistamab plus nirogacestat.

Group V: Treatment Regimen B: Teclistamab + Daratumumab + Lenalidomide + Bortezomib (21-day Cycles) Experimental Treatment 4 Interventions

Participants will receive teclistamab plus daratumumab plus lenalidomide plus bortezomib in 21-day cycles.

Group VI: Treatment Regimen A: Teclistamab + Daratumumab + Pomalidomide Experimental Treatment 3 Interventions

Participants will receive teclistamab plus daratumumab plus pomalidomide.

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

Approved in United States as Tecvayli for:

• Relapsed or refractory multiple myeloma in adults who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody

Approved in European Union as Tecvayli for:

• Relapsed or refractory multiple myeloma in adults who have received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody, and have demonstrated disease progression since the last therapy

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

Teclistamab-cqyv is a bispecific T-cell engager antibody that effectively activates the immune system to target multiple myeloma cells, showing an overall response rate of over 60% in heavily pretreated patients.

The side effect profile of teclistamab-cqyv is more tolerable compared to other BCMA-targeted therapies, making it a suitable treatment option for elderly patients with relapsed or refractory multiple myeloma, and it has received FDA approval for use as monotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teclistamab-cqyv: The First Bispecific T-Cell Engager Antibody for the Treatment of Patients With Relapsed or Refractory Multiple Myeloma. Hua, G., Scanlan, R., Straining, R., et al.[2023]

Teclistamab-cqyv is an FDA and EMA-approved bispecific antibody that effectively targets multiple myeloma (MM) by engaging T cells to attack cancer cells, showing a 60% overall response rate in heavily pretreated relapsed/refractory patients.

This treatment is specifically designed for patients who have undergone at least three prior therapies and have shown disease progression, highlighting its role in advanced stages of MM where other treatments have failed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teclistamab-cqyv in multiple myeloma. Martino, EA., Bruzzese, A., Labanca, C., et al.[2023]

Teclistamab, a bispecific antibody targeting B-cell maturation antigen and CD3, has shown promising efficacy in treating relapsed/refractory multiple myeloma, with the recommended Phase II dose established at 1.5 mg/kg subcutaneously, which maintains drug levels above the effective concentration needed for maximum cytotoxicity.

The study utilized pharmacokinetic modeling to predict effective dosing ranges, confirming that doses of 0.27 mg/kg and 0.72 mg/kg intravenously, as well as 0.72 mg/kg subcutaneously, achieved serum concentrations that correlate with effective treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Translational Modeling Predicts Efficacious Therapeutic Dosing Range of Teclistamab for Multiple Myeloma. Girgis, S., Lin, SXW., Pillarisetti, K., et al.[2022]

Teclistamab has demonstrated strong anti-myeloma activity in patients who have severe renal impairment, indicating its potential effectiveness in a challenging patient population.

The study highlights the importance of evaluating treatments like teclistamab for their efficacy in patients with specific health conditions, such as renal issues, which can complicate cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teclistamab in patients with multiple myeloma and impaired renal function. Joiner, L., Bal, S., Godby, KN., et al.[2023]

Teclistamab, a bispecific antibody targeting CD3 and BCMA, has received conditional approval in the EU and full approval in the US for treating adult patients with relapsed or refractory multiple myeloma after multiple prior therapies.

The approvals are based on its efficacy in patients who have undergone at least three to four previous treatments, including specific types of therapies, highlighting its role as a treatment option for difficult-to-treat cases of multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teclistamab: First Approval. Kang, C.[2022]

Teclistamab is the first bispecific antibody approved for treating relapsed or refractory multiple myeloma, showing impressive efficacy in heavily pretreated patients, making it a promising option in this challenging area of treatment.

While teclistamab offers significant benefits, it also has notable adverse effects such as cytokine release syndrome, infections, and neurotoxicity, requiring careful management and precautions by healthcare providers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Teclistamab for Multiple Myeloma: Clinical Insights and Practical Considerations for a First-in-Class Bispecific Antibody. Pan, D., Richter, J.[2023]

Multiple myeloma is a promising target for immune therapies due to its unique plasma cell biology and bone marrow environment, allowing for treatments that can selectively kill cancer cells with minimal side effects.

Recent advancements in immune therapies, including immune modulatory drugs, targeted antibodies, CAR-T cell therapies, and vaccines, have led to improved treatment options with enhanced effectiveness and specificity against multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Keeping Myeloma in Check: The Past, Present and Future of Immunotherapy in Multiple Myeloma. Ackley, J., Ochoa, MA., Ghoshal, D., et al.[2023]

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]

References

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

Teclistamab-cqyv: The First Bispecific T-Cell Engager Antibody for the Treatment of Patients With Relapsed or Refractory Multiple Myeloma. [2023]

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

Teclistamab-cqyv in multiple myeloma. [2023]

3. France pubmed.ncbi.nlm.nih.gov

Translational Modeling Predicts Efficacious Therapeutic Dosing Range of Teclistamab for Multiple Myeloma. [2022]

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

Teclistamab in patients with multiple myeloma and impaired renal function. [2023]

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

Teclistamab: First Approval. [2022]

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

Teclistamab for Multiple Myeloma: Clinical Insights and Practical Considerations for a First-in-Class Bispecific Antibody. [2023]

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

New strategies in the treatment of multiple myeloma. [2021]

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

Emerging drugs and combinations to treat multiple myeloma. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Keeping Myeloma in Check: The Past, Present and Future of Immunotherapy in Multiple Myeloma. [2023]

10. Netherlands pubmed.ncbi.nlm.nih.gov

Evidence-based mechanisms of synergy with IMiD agent-based combinations in multiple myeloma. [2023]

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

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