Teclistamab Dosing for Multiple Myeloma

(MajesTEC-1 Trial)

Not currently recruiting at 19 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Janssen Research & Development, LLC

Must not be taking: BCMA targeted therapy

Disqualifiers: Active 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: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Teclistamab, a monoclonal antibody, for people with multiple myeloma, a type of blood cancer. The goal is to determine a safe dose and schedule for the medication and to assess its tolerability. Participants will be divided into groups; some will receive the medication subcutaneously, while others will receive it intravenously. The trial seeks participants with multiple myeloma that has recurred or not responded to other treatments, including proteasome inhibitors and monoclonal antibodies. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

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.

Is there any evidence suggesting that Teclistamab is likely to be safe for humans?

Research has shown that Teclistamab has been tested for safety in adults with relapsed or hard-to-treat multiple myeloma. In the MajesTEC-1 study, 165 patients received Teclistamab. It was generally well-tolerated, but some side effects occurred, including cytokine release syndrome (CRS), where the immune system becomes overly active, and nervous system problems.

For the intravenous (IV) form of Teclistamab, similar safety concerns arose. Serious side effects like CRS and nervous system issues were noted, although many patients continued treatment for six months or more.

While Teclistamab shows promise, discussing potential risks and benefits with a healthcare provider before joining a trial is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Unlike the standard treatments for multiple myeloma, which typically include chemotherapy, proteasome inhibitors, and immunomodulatory drugs, Teclistamab offers a novel approach by targeting BCMA (B-cell maturation antigen), a protein commonly found on myeloma cells. Researchers are excited about Teclistamab because it acts as a bispecific antibody, engaging both the myeloma cells and the patient's T-cells, effectively directing the immune system to attack the cancer. Additionally, Teclistamab can be administered both subcutaneously and intravenously, providing flexibility in treatment methods that could improve patient comfort and convenience. These features make Teclistamab a promising option for patients who might not respond well to existing therapies.

What evidence suggests that Teclistamab might be an effective treatment for multiple myeloma?

Research has shown that teclistamab holds promise for treating multiple myeloma, a type of blood cancer. Studies found that 65% of patients experienced a partial response or better, indicating improvement in their cancer. In 28% of cases, patients achieved a complete response, with no detectable signs of cancer. The treatment kept the cancer under control for an average of 11.3 months, and patients lived for an average of 18.3 months after starting treatment. These results suggest teclistamab could be effective for those with relapsed or hard-to-treat multiple myeloma. Participants in this trial will receive teclistamab either subcutaneously or intravenously, as part of different dosing strategies under evaluation. ^{3 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 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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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

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]

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-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 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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12198414/

Outcomes of teclistamab in patients with relapsed/ ...

Data describing outcomes of teclistamab in multiple myeloma patients with prior exposure to BCMA-directed therapy (BCMA-DT) are limited.

2.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2203478

Teclistamab in Relapsed or Refractory Multiple Myeloma

At this dose level, teclistamab showed promising efficacy in 40 patients, with 65% of patients having a partial response or better. Here, we report the efficacy ...

3.

tecvaylihcp.com

tecvaylihcp.com/clinical-study-results/

Clinical Study Results | TECVAYLI® (teclistamab-cqyv) HCP

The efficacy of TECVAYLI® was evaluated in 110 patients with relapsed or refractory multiple myeloma in the single-arm, open-label, multi-center, phase 1/2 ...

4.

ashpublications.org

ashpublications.org/blood/article/144/23/2375/517467/Efficacy-and-safety-of-teclistamab-in-patients

Efficacy and safety of teclistamab in patients with relapsed ...

The MajesTEC-1 trial cohort C results demonstrate favorable efficacy and safety of teclistamab in patients with heavily pretreated R/RMM and ...

5.

jnj.com

jnj.com/media-center/press-releases/tecvayli-teclistamab-cqyv-shows-sustained-deep-and-durable-responses-in-patients-with-relapsed-or-refractory-multiple-myeloma

TECVAYLI® (teclistamab-cqyv) shows sustained deep and ...

New MajesTEC-1 data show a median duration of response of 24 months, with responses deepening, including in patients who switched to ...

6.

tecvaylihcp.com

tecvaylihcp.com/safety-profile/

Safety Profile - TECVAYLI® (teclistamab-cqyv) HCP

Among patients who received TECVAYLI®, 47% were exposed for 6 months or longer and 7% were exposed for one year or longer.

7.

tecvayli.com

tecvayli.com/dosing-and-side-effects/side-effects/

Side Effects | TECVAYLI® (teclistamab-cqyv)

TECVAYLI® may cause side effects that are serious, life-threatening, or lead to death, including Cytokine Release Syndrome (CRS) and neurologic problems.

8.

ema.europa.eu

ema.europa.eu/en/documents/product-information/tecvayli-epar-product-information_en.pdf

Tecvayli, INN-teclistamab - EMA

The safety data of TECVAYLI was evaluated in MajesTEC-1, which included 165 adult patients with multiple myeloma who received the recommended dosing regimen of ...

9.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2022/761291s000lbl.pdf

TECVAYLI. Teclistamab - accessdata.fda.gov

The safety of TECVAYLI was evaluated in MajesTEC-1 [see Clinical Studies (14)] which included adult patients with relapsed or refractory multiple myeloma.