Talquetamab + Teclistamab for Multiple Myeloma

(RedirecTT-1 Trial)

Recruiting at 54 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Janssen Research & Development, LLC

Must not be taking: Targeted therapy, Epigenetic therapy

Disqualifiers: CNS involvement, Plasma cell leukemia, others

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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Until completion of the end of treatment visit

228 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of two drugs, talquetamab and teclistamab, in patients whose multiple myeloma has come back or did not respond to previous treatments. The drugs aim to destroy cancer cells by targeting specific proteins on their surface.

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 cannot have had targeted therapy, epigenetic therapy, or investigational treatments within 21 days before starting the study treatment.

What data supports the effectiveness of the drug combination Talquetamab and Teclistamab for treating multiple myeloma?

Talquetamab has shown significant anticancer effects in nearly three-quarters of patients with relapsed or refractory multiple myeloma in a clinical trial, while Teclistamab has demonstrated an overall response rate of more than 60% in heavily pretreated patients. Both drugs activate the immune system to target cancer cells, suggesting their potential effectiveness when used together. ^{1 2 3 4 5}

What safety data exists for Talquetamab and Teclistamab in treating multiple myeloma?

Daratumumab, used in combination therapies for multiple myeloma, has shown minimal overall toxicity with common side effects like low blood cell counts. Talquetamab and Teclistamab, both approved for multiple myeloma, have side effects including infusion reactions, infections, and neurotoxicity, but are generally considered tolerable with proper precautions. ^{1 2 4 6 7}

What makes the drug combination of Talquetamab, Teclistamab, and Daratumumab unique for treating multiple myeloma?

This drug combination is unique because it includes Talquetamab and Teclistamab, which are both bispecific antibodies that engage T-cells to target specific proteins on multiple myeloma cells, offering a novel approach for patients who have relapsed or are resistant to other treatments. Talquetamab targets GPRC5D, while Teclistamab targets BCMA, and both have shown promising results in heavily pretreated patients. ^{1 2 4 8 9}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for people with multiple myeloma that's come back or hasn't responded to treatment. They should be able to perform daily activities without significant issues (ECOG grade 0-1). Participants must have been diagnosed according to specific criteria and can't join if they've had certain other conditions, recent experimental therapies, or a stem cell transplant within the last six months.

Inclusion Criteria

I am fully active or restricted in physically strenuous activity but can do light work.

My multiple myeloma diagnosis follows international guidelines.

My condition did not improve or worsened after the last treatment.

Exclusion Criteria

I had a stem cell transplant from a donor within the last 6 months.

I haven't had targeted, epigenetic, or investigational treatments recently.

I have a specific blood cancer or related condition.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Treatment

Participants receive the study drug combination of talquetamab and teclistamab, with or without daratumumab, in 28-day cycles

Until completion of the end of treatment visit

Follow-up

Participants are monitored for safety and effectiveness after treatment

16 weeks

Long-term follow-up

Participants are monitored for long-term outcomes and survival

Up to 5 years

Treatment Details

Interventions

• Daratumumab
• Talquetamab
• Teclistamab

Trial Overview The study is testing combinations of Talquetamab and Teclistamab in those with relapsed or refractory multiple myeloma. It aims to find the best dose and schedule, assess safety at this dose, and see how well these drugs work against cancer, especially when it has spread outside the bone marrow.

Participant Groups

Group I: Part 3: Phase 2 Experimental Treatment 2 Interventions

Participants will receive teclistamab + talquetamab combination therapy, at the RP2R selected from Part 1 and Part 2.

Group II: Part 2: Dose Expansion Experimental Treatment 3 Interventions

Participants will receive treatment doses (combination of tal+tec and dara+tal+tec regimens) which will be determined by the recommended Phase 2 regimen (s) (RP2R\[s\]) of the study treatment identified in Part 1.

Group III: Part 1: Dose Escalation Experimental Treatment 3 Interventions

Participants will receive tec+tal with or without daratumumab in 28-day cycles following initial step-up doses.

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

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]

Talquetamab, a bispecific T-cell engager targeting GPRC5D and CD3, has received accelerated approval in the USA and conditional marketing authorization in the EU for treating adults with relapsed or refractory multiple myeloma, highlighting its potential as a new treatment option.

This approval marks a significant milestone in the development of talquetamab, indicating its efficacy and safety in addressing a challenging form of cancer that has not responded to previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talquetamab: First Approval. Keam, SJ.[2023]

Daratumumab is a monoclonal antibody that effectively targets CD38 on multiple myeloma cells, leading to cell death through various mechanisms such as complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity.

It has shown a favorable safety profile and significant clinical activity as both a standalone treatment and in combination with lenalidomide for patients with relapsed multiple myeloma who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. Xia, C., Ribeiro, M., Scott, S., et al.[2018]

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]

In the MonumenTAL-1 trial, nearly 75% of the 288 patients with relapsed/refractory multiple myeloma showed significant anticancer effects from the investigational drug talquetamab.

Talquetamab is a first-in-class bispecific antibody that targets GPRC5D on malignant plasma cells while sparing normal cells, effectively activating T cells to mount an immune response against the cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MonumenTAL Results for Talquetamab in Myeloma. [2023]

Daratumumab, when combined with lenalidomide and dexamethasone or bortezomib and dexamethasone, significantly improves progression-free survival in patients with multiple myeloma who have received prior therapy, with reductions in the risk of disease progression or death by 63% and 61%, respectively.

The most common side effects reported were infusion reactions, diarrhea, and upper respiratory infections, with neutropenia and thrombocytopenia noted as important warnings, indicating that while daratumumab is effective, monitoring for these adverse reactions is essential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Daratumumab for Treatment of Multiple Myeloma After One Prior Therapy. Bhatnagar, V., Gormley, NJ., Luo, L., et al.[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]

Talquetamab, a bispecific antibody targeting GPRC5D and CD3, shows similar efficacy and durability of response in treating relapsed or refractory multiple myeloma compared to teclistamab, the first bispecific antibody approved for this condition.

While talquetamab has a lower incidence of infections than teclistamab, it presents unique side effects related to skin, oral, and nails, yet remains a well-tolerated and effective treatment option for patients with heavily pretreated multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Talquetamab in multiple myeloma. Liu, L., Krishnan, A.[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]

References

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

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

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

Talquetamab: First Approval. [2023]

3. Spain pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. [2018]

4. 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]

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

MonumenTAL Results for Talquetamab in Myeloma. [2023]

6. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Daratumumab for Treatment of Multiple Myeloma After One Prior Therapy. [2022]

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

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

8. Italy pubmed.ncbi.nlm.nih.gov

Talquetamab in multiple myeloma. [2023]

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

Teclistamab: First Approval. [2022]