Talquetamab Combinations for Multiple Myeloma

(MonumenTAL-6 Trial)

Recruiting at 242 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Stroke, Seizure, Major surgery, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 6 years 5 months

795 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing two new drug combinations to treat multiple myeloma. The combinations include talquetamab with either pomalidomide or teclistamab. These drugs help the immune system better identify and destroy cancer cells. The goal is to see if these new combinations work better than existing treatments.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug Talquetamab 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, and it has been granted accelerated approval in the USA and conditional marketing authorization in the EU for this condition. ^{1 2 3 4 5}

Is Talquetamab safe for humans?

Talquetamab has been shown to be generally well-tolerated in clinical trials for multiple myeloma, with fewer infections compared to similar treatments, but it can cause side effects like skin, mouth, and nail issues. Teclistamab, a similar drug, has side effects such as cytokine release syndrome (a severe immune reaction), infections, and nerve problems, but is considered more tolerable for older patients. ^{1 2 3 6 7}

What makes the drug Talquetamab combined with Teclistamab unique for treating multiple myeloma?

Talquetamab and Teclistamab are unique because they are bispecific antibodies that engage T-cells to target specific proteins on multiple myeloma cells, with Talquetamab targeting GPRC5D and Teclistamab targeting BCMA. This dual targeting approach is novel and offers a new option for patients who have relapsed or are resistant to other treatments. ^{1 2 3 6 8}

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 has come back or hasn't responded to treatment, including an anti-CD38 antibody and lenalidomide. Participants should be fairly active (ECOG score of 0-2), not pregnant or planning pregnancy soon, and have measurable disease levels according to specific medical criteria.

Inclusion Criteria

You cannot be pregnant, breastfeeding, or planning to get pregnant during the study or within 6 months after the study treatment.

My cancer came back or didn't respond well to treatment.

I have been diagnosed with multiple myeloma and meet the specific blood or urine test criteria.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Talquetamab plus Pomalidomide (Tal-P), Talquetamab plus Teclistamab (Tal-Tec), or Investigator's choice of Elotuzumab, Pomalidomide, and Dexamethasone (EPd) or Pomalidomide, Bortezomib, and Dexamethasone (PVd)

Up to 6 years 5 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Talquetamab
• Teclistamab

Trial Overview The study compares the effectiveness of talquetamab with pomalidomide (Tal-P) or talquetamab with teclistamab (Tal-Tec) against two other drug combinations: elotuzumab with pomalidomide and dexamethasone (EPd), or pomalidomide with bortezomib and dexamethasone (PVd).

Participant Groups

Group I: Arm B: Talquetamab + Teclistamab (Tal-Tec) Experimental Treatment 3 Interventions

Participants will receive teclistamab in combination with talquetamab both as SC injection; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug.

Group II: Arm A: Talquetamab + Pomalidomide (Tal-P) Experimental Treatment 3 Interventions

Participants will receive talquetamab as subcutaneous (SC) injections; pomalidomide will be self-administered as a single dose orally; dexamethasone may be given orally or intravenously as a pretreatment medication and study drug.

Group III: Arm C: Elotuzumab+ Pomalidomide+Dexamethasone (EPd) or Pomalidomide+Bortezomib+Dexamethasone (PVd) Active Control 4 Interventions

Participants will either receive elotuzumab intravenous (IV) injection in combination with pomalidomide and dexamethasone orally; or pomalidamide orally in combination with bortezomib SC injection and dexamethasone orally as per investigator choice. Dexamethasone will be administered as a pretreatment medication.

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

Approved in United States as Talquetamab for:

• Relapsed or refractory multiple myeloma

Approved in European Union as Talquetamab for:

• Relapsed or refractory multiple myeloma

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]

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]

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]

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]

The treatment landscape for relapsed/refractory multiple myeloma has evolved significantly with the introduction of various therapies, including the first-in-class BCMA-directed bispecific antibody teclistamab, highlighting the importance of understanding therapy selection and sequencing due to the complexity of available options.

Ongoing clinical trials for new agents like elranatamab and talquetamab show promise for future treatments, but considerations around tolerability, the aging population, and financial implications are crucial for optimizing patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emerging therapeutic landscape of relapsed/refractory multiple myeloma. Tanenbaum, B., Miett, T., Patel, SA.[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 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, 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. 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

Talquetamab: First Approval. [2023]

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

Teclistamab-cqyv in multiple myeloma. [2023]

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

MonumenTAL Results for Talquetamab in Myeloma. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

The emerging therapeutic landscape of relapsed/refractory multiple myeloma. [2023]

6. Italy pubmed.ncbi.nlm.nih.gov

Talquetamab in multiple myeloma. [2023]

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

Teclistamab: First Approval. [2022]