Teclistamab Combination Therapy for Multiple Myeloma

(MajesTEC-2 Trial)

Not currently recruiting at 39 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and optimal dosage of teclistamab, an experimental treatment, in combination with other therapies for multiple myeloma, a type of blood cancer. Several treatment combinations are under evaluation, including teclistamab with drugs like daratumumab and lenalidomide. The trial aims to determine which combination is most effective for patients at different stages of the disease, whether newly diagnosed or relapsed. Individuals with a confirmed diagnosis of multiple myeloma who have tried other therapies and still have active disease may be suitable candidates for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

In previous studies, the combination of teclistamab with daratumumab and lenalidomide showed a manageable side effect profile, meaning most patients did not experience severe negative reactions. Patients generally tolerated the combination well and showed early positive responses to treatment.

Research on teclistamab with daratumumab, lenalidomide, and bortezomib also supports its safety, with patients typically managing the treatment's side effects, indicating general tolerability.

For the combination of teclistamab with daratumumab and pomalidomide, studies reported that most patients found the treatment manageable, with no unexpected adverse effects.

Early findings suggest that the combination of teclistamab and nirogacestat is safe, with patients experiencing positive treatment effects and manageable side effects.

Finally, teclistamab with lenalidomide has demonstrated a good safety profile, with patients generally tolerating the combination well and continuing treatment without severe issues.

Overall, these combinations of teclistamab with other treatments have been well-received in studies, with most patients handling them without significant problems. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about teclistamab combination therapies for multiple myeloma because they offer a fresh approach compared to traditional treatments like proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. Teclistamab is a bispecific antibody, which means it can engage two different targets at once, specifically binding to both a protein on myeloma cells and T-cells, effectively directing the immune system to attack the cancer. Some treatment regimens also incorporate additional drugs like daratumumab, lenalidomide, pomalidomide, and bortezomib, which have shown success individually and are now combined to potentially enhance efficacy. This innovative mechanism and the strategic combination of drugs aim to improve outcomes for patients who may not respond well to existing therapies.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research shows that teclistamab, especially when combined with other treatments, holds great promise for treating multiple myeloma. In this trial, participants may receive teclistamab with daratumumab and lenalidomide, which studies have found can significantly extend the time patients live without their disease worsening. Another treatment arm includes bortezomib in addition to teclistamab, daratumumab, and lenalidomide, effectively delaying disease progression. Notably, participants in a different arm receiving teclistamab with nirogacestat have shown high response rates in patients whose disease returned after other treatments. Overall, these combinations enhance treatment responses and may offer new hope for those battling multiple myeloma. ^{1 3 4 6 7}

Who Is on the Research Team?

Janssen Research and Development, LLC Clinical Trial

Principal Investigator

Janssen Research and Development LLC

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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

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]

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 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 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-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]

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, 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]

Citations

1. jnj.com jnj.com/media-center/press-releases/tecvayli-plus-darzalex-faspro-combination-regimen-significantly-improves-progression-free-survival-and-overall-survival-versus-standard-of-care

TECVAYLI® plus DARZALEX FASPRO® combination ... The study evaluates the efficacy and safety of TECVAYLI® (teclistamab-cqyv) in combination with DARZALEX FASPRO® (daratumumab and hyaluronidase- ...

2. myeloma.org myeloma.org/news-events/multiple-myeloma-news/phase-3-majestec-3-tecvayli-darzalex-results

Phase 3 MajesTEC-3 Results: Tecvayli-Darzalex Faspro ... At follow-up after almost three years, treatment with TECVAYLI and DARZALEX FASPRO showed significant delayed progression of multiple myeloma ...

3. onclive.com onclive.com/view/teclistamab-based-induction-regimens-deepen-responses-in-newly-diagnosed-multiple-myeloma

Teclistamab-Based Induction Regimens Deepen ... Marc S. Raab, MD, discusses updated MRD negativity and safety data with teclistamab plus SOC induction regimens in newly diagnosed multiple ...

4. oncologypipeline.com oncologypipeline.com/apexonco/jj-claims-tecvaylidarzalex-combo-win

J&J claims a Tecvayli/Darzalex combo win | ApexOnco At ASCO 2024 the company presented results from a safety run-in phase, which showed a 92% ORR with Tecvayli plus Darzalex plus Revlimid. J&J ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10171572/

P30 SINGLE COHORT RESULTS FROM MAJESTEC-2 Both DARA and LEN have immunomodulatory effects that may enhance the function of TEC, potentially resulting in improved antimyeloma activity in a broader ...

6. ashpublications.org ashpublications.org/ashclinicalnews/news/7960/Teclistamab-Combination-with-Daratumumab

Teclistamab Combination with Daratumumab, Lenalidomide ... The triple combination of teclistamab plus daratumumab and lenalidomide had an acceptable side effect profile and showed early efficacy among transplant- ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05552222

NCT05552222 | A Study of Teclistamab in Combination ... The purpose of this study is to compare the efficacy of teclistamab in combination with daratumumab and lenalidomide (Tec-DR) and talquetamab in combination ...