Talquetamab Combination Therapy for Multiple Myeloma

(MonumenTAL-2 Trial)

Recruiting at 36 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: CNS involvement, HIV, Stroke, 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: 7 weeks

166 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to characterize the safety and tolerability of talquetamab when administered in different combination regimens and to identify the safe dose(s) of talquetamab combination regimens.

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?

In the MonumenTAL-1 trial, nearly 75% of patients with relapsed or refractory multiple myeloma experienced significant anticancer effects with Talquetamab. This drug targets specific proteins on cancer cells and activates the immune system to fight the cancer. ^{1 2 3 4 5}

Is Talquetamab safe for humans?

Talquetamab has been shown to be generally well-tolerated in humans, with some unique side effects like skin, oral, and nail issues. It has fewer infections compared to similar treatments and is considered a promising therapy for multiple myeloma. ^{2 3 4 6 7}

What makes the drug Talquetamab unique for treating multiple myeloma?

Talquetamab is unique because it is a first-in-class bispecific antibody that targets a specific protein (GPRC5D) found on cancerous plasma cells and recruits T-cells to attack these cells, offering a new approach for patients with relapsed or refractory multiple myeloma. ^{2 3 4 5 8}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

This trial is for individuals with confirmed multiple myeloma who can follow the study's lifestyle restrictions, including pregnancy prevention plans. They must have measurable disease indicators and be in good physical condition (ECOG score of 0 or 1). Women of childbearing potential need a negative pregnancy test before starting treatment.

Inclusion Criteria

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

If you are a woman who could become pregnant, you need to have a negative pregnancy test before starting the study treatment.

You have specific levels of proteins in your blood or urine that indicate the presence of the disease.

Exclusion Criteria

I have not had a stroke or seizure in the last 6 months.

I have or might have myeloma affecting my brain or spinal cord.

I have taken a high dose of steroids equivalent to 140 mg of prednisone or more in the last two weeks.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive talquetamab in combination with other anticancer therapies to assess safety and tolerability

7 weeks

Multiple visits for administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 1 year and 10 months

Treatment Details

Interventions

• Talquetamab

Trial Overview The study tests Talquetamab combined with other cancer drugs like Carfilzomib, Daratumumab SC, Lenalidomide, and Pomalidomide to find safe doses and assess safety. It aims to understand how well these combinations work for treating multiple myeloma.

Participant Groups

Group I: Treatment Regimen E: Talquetamab + Pomalidomide Experimental Treatment 2 Interventions

Participants assigned to Treatment regimen E will receive talquetamab SC in combination with pomalidomide orally.

Group II: Treatment Regimen D: Talquetamab + Daratumumab + Lenalidomide Experimental Treatment 3 Interventions

Participants assigned to Treatment regimen D will receive talquetamab SC in combination with daratumumab SC and lenalidomide orally.

Group III: Treatment Regimen C: Talquetamab + Lenalidomide Experimental Treatment 2 Interventions

Participants assigned to Treatment regimen C will receive talquetamab SC in combination with lenalidomide orally.

Group IV: Treatment Regimen B: Talquetamab + Daratumumab + Carfilzomib Experimental Treatment 3 Interventions

Participants assigned to Treatment regimen B will receive talquetamab SC in combination with daratumumab SC and carfilzomib as an IV infusion.

Group V: Treatment Regimen A: Talquetamab + Carfilzomib Experimental Treatment 2 Interventions

Participants assigned to Treatment regimen A will receive talquetamab subcutaneously (SC) in combination with carfilzomib as an intravenous (IV) infusion.

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

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]

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]

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]

In the phase 1 MonumenTAL-1 study involving patients with refractory or relapsed multiple myeloma, two doses of talquetamab (405 μg/kg weekly and 800 μg/kg every other week) were found to be well tolerated, with most side effects being mild or moderate, including cytokine release syndrome (CRS).

The treatment showed promising efficacy, with most participants experiencing a reduction in cancer signs and a median duration of response of 8-10 months, indicating talquetamab's potential as a new option for patients who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Plain language summary of the MonumenTAL-1 study of talquetamab in people with relapsed or refractory multiple myeloma. Chari, A., Askari, E., Caers, J., et al.[2023]

Three new bispecific antibodies—teclistamab, elranatamab, and talquetamab—have received accelerated FDA approval for treating relapsed/refractory multiple myeloma, indicating their potential efficacy in this challenging condition.

While these agents show promise, the medical community is currently awaiting results from randomized phase III clinical trials to better understand their effectiveness compared to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Embarrassment of Riches: Three FDA-Approved Bispecific Antibodies for Relapsed Refractory Multiple Myeloma. Firestone, R., Lesokhin, AM., Usmani, SZ.[2023]

References

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

New insights into therapeutic targets in myeloma. [2016]

2. Italy pubmed.ncbi.nlm.nih.gov

Talquetamab in multiple myeloma. [2023]

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

Talquetamab: First Approval. [2023]

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

MonumenTAL Results for Talquetamab in Myeloma. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Plain language summary of the MonumenTAL-1 study of talquetamab in people with relapsed or refractory multiple myeloma. [2023]

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

An Embarrassment of Riches: Three FDA-Approved Bispecific Antibodies for Relapsed Refractory Multiple Myeloma. [2023]

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

Preclinical activity and determinants of response of the GPRC5DxCD3 bispecific antibody talquetamab in multiple myeloma. [2021]

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

2-[ 18 F]FDG PET/CT Flare-up Phenomena Following T-Cell Engager Bispecific Antibody in Multiple Myeloma. [2023]