Teclistamab Dosing for Multiple Myeloma

(MajesTEC-1 Trial)

Recruiting at 18 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Janssen Research & Development, LLC

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: 1

302 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to identify the recommended Phase 2 dose(s) (RP2Ds) and schedule assessed to be safe for Teclistamab and to characterize the safety and tolerability of Teclistamab at the RP2Ds.

Will I have to stop taking my current medications?

The trial requires stopping certain medications before starting the study drug. You must stop monoclonal antibody treatments 21 days before, proteasome inhibitors 14 days before, and immunomodulatory agents 7 days before the first dose of the study drug.

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

Teclistamab has shown effectiveness in treating multiple myeloma, with a clinical trial demonstrating an overall response rate of more than 60% in patients who had already tried several other treatments. It is approved for use in patients with relapsed or refractory multiple myeloma, meaning their cancer has returned or not responded to previous treatments. ^{1 2 3 4 5}

Is teclistamab 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 (nerve damage). However, it is considered more tolerable for elderly patients compared to other similar treatments. ^{1 2 3 4 5}

How is the drug Teclistamab unique in treating multiple myeloma?

Teclistamab is unique because it is a bispecific antibody that targets both BCMA (B-cell maturation antigen) on myeloma cells and CD3 on T cells, helping the immune system directly attack the cancer cells. This mechanism of action is different from traditional treatments like chemotherapy or immunomodulatory drugs, which do not specifically engage T cells in this way. ^{6 7 8 9 10}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for adults with multiple myeloma that's come back or hasn't responded to standard treatments, including a proteasome inhibitor, an immunomodulatory drug, and anti-CD38 antibody. They must be in good physical condition (ECOG score of 0 or 1), able to use birth control if necessary, and give informed consent. People who've had BCMA-targeted therapy or certain recent cancer treatments can't join.

Inclusion Criteria

Participants must sign an ICF indicating that he or she understands the purpose of and procedures required for the study and is willing to participate in the study. Consent is to be obtained prior to the initiation of any study-related tests or procedures that are not part of standard-of-care for the participant's disease

My multiple myeloma has not responded to or I cannot tolerate standard treatments, and I've been treated with a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody.

I am using birth control as a woman who can still have children.

Exclusion Criteria

I have taken a high dose of steroids recently.

My multiple myeloma has spread to my brain or spinal cord.

Side effects from my past cancer treatments have mostly gone away.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

1 visit (in-person)

Dose Escalation

Participants receive Teclistamab either subcutaneously or intravenously to determine the recommended Phase 2 dose(s) and assess safety and tolerability

Up to 28 days

Multiple visits (in-person)

Dose Expansion

Participants receive Teclistamab at the recommended Phase 2 dose(s) to further evaluate safety, tolerability, and preliminary antitumor activity

Approximately 91 days

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 7 years and 3 months

Periodic visits (in-person)

Treatment Details

Interventions

• Teclistamab

Trial Overview The study tests Teclistamab given through IV or under the skin (SC) to find safe doses for Phase 2 trials. It aims to understand how well patients tolerate these doses while monitoring safety and side effects during treatment.

Participant Groups

Group I: Part 2: Dose Expansion (SC) Experimental Treatment 1 Intervention

Participants will receive Teclistamab SC.

Group II: Part 2: Dose Expansion (IV) Experimental Treatment 1 Intervention

Participants will receive Teclistamab IV.

Group III: Part 1: Dose Escalation (SC) Experimental Treatment 1 Intervention

Participants will receive Teclistamab subcutaneously (SC).

Group IV: Part 1: Dose Escalation (IV) Experimental Treatment 1 Intervention

Participants will receive Teclistamab intravenously (IV).

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, 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-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 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]

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]

In patients with newly diagnosed multiple myeloma, the modified regimen of bortezomib, thalidomide, and dexamethasone (VTd-mod) using a lower thalidomide dose (100 mg/day) was found to be noninferior to the traditional higher dose (VTd-label) in terms of overall survival and progression-free survival, while showing better post-transplant response rates.

The combination of daratumumab with the VTd regimen (D-VTd) demonstrated superior efficacy compared to the traditional VTd-label, while maintaining similar safety profiles, supporting its use as a first-line treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative efficacy and safety of bortezomib, thalidomide, and dexamethasone (VTd) without and with daratumumab (D-VTd) in CASSIOPEIA versus VTd in PETHEMA/GEM in transplant-eligible patients with newly diagnosed multiple myeloma, using propensity score matching. Moreau, P., Hulin, C., Zweegman, S., 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. New Zealand pubmed.ncbi.nlm.nih.gov

Teclistamab: First Approval. [2022]

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

Teclistamab-cqyv in multiple myeloma. [2023]

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

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

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

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

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

Comparative efficacy and safety of bortezomib, thalidomide, and dexamethasone (VTd) without and with daratumumab (D-VTd) in CASSIOPEIA versus VTd in PETHEMA/GEM in transplant-eligible patients with newly diagnosed multiple myeloma, using propensity score matching. [2023]

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

High dose chemotherapy in light chain or light and heavy chain deposition disease. [2013]

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

T cells expressing an anti-B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Frequent good partial remissions from thalidomide including best response ever in patients with advanced refractory and relapsed myeloma. [2019]

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

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