Talquetamab Combination Therapy for Multiple Myeloma

(MonumenTAL-2 Trial)

Not currently recruiting at 41 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and tolerability of the drug talquetamab (Talvey) when combined with other medications for treating multiple myeloma, a type of blood cancer. Participants will receive talquetamab in various combinations, including with pomalidomide, daratumumab, lenalidomide, and carfilzomib. Individuals diagnosed with multiple myeloma who can measure their disease levels through specific tests might be suitable candidates for the trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the chance 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. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that talquetamab, whether used alone or with other drugs, holds promise in treating multiple myeloma, a type of blood cancer. Safety data indicate that many patients experience mild to moderate side effects, known as Grade 1 and 2, which are generally manageable. Specifically, 78.8% of patients report these milder side effects.

The combination of talquetamab and pomalidomide has been studied, and early results suggest it is safe with tolerable side effects. Trials have shown that combining talquetamab with daratumumab and lenalidomide is effective, with manageable safety concerns and a high response rate in patients.

Similarly, when talquetamab is paired with daratumumab and carfilzomib, or with lenalidomide alone, the safety data remain consistent, showing manageable side effects. Some studies have demonstrated positive outcomes with these combinations in patients who have already undergone several treatments.

Overall, the FDA has approved talquetamab for other conditions, supporting its safety. However, since this is an early-phase study, ongoing trials are needed to better understand its safety when combined with other drugs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about talquetamab for multiple myeloma because it introduces a novel approach by targeting the GPRC5D protein, a new mechanism of action compared to existing treatments like bortezomib, lenalidomide, or daratumumab. Unlike traditional options, talquetamab is administered subcutaneously, which may offer more convenience and potentially fewer side effects. Combining talquetamab with other drugs like pomalidomide, daratumumab, lenalidomide, or carfilzomib aims to enhance effectiveness and provide new hope for patients who may not respond well to current therapies.

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

This trial will evaluate various combinations of talquetamab for treating multiple myeloma. Research has shown that talquetamab, when used with pomalidomide, helped 63% of patients, with more than half experiencing a very good improvement. One arm of this trial will test talquetamab with pomalidomide. Another arm will test talquetamab combined with daratumumab and lenalidomide, which has shown extremely effective results, with some studies reporting up to a 100% response rate. The combination of talquetamab with daratumumab and carfilzomib, tested in a separate arm, demonstrated a response rate of about 74%, indicating consistent effectiveness. Talquetamab with lenalidomide, also tested in this trial, showed a strong response rate of around 63%, similar to the results with pomalidomide. Lastly, when paired with carfilzomib, talquetamab continued to show high response rates, further supporting its potential in treating multiple myeloma. Each of these combinations shows promising results, suggesting that talquetamab may be effective in treating this condition. ^{1 2 3 5 6}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

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

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11798766/

Talquetamab in Multiple Myeloma: Efficacy, Safety, and Future ... The real‐world data further support talquetamab's efficacy, making it a valuable addition to the RRMM treatment landscape. Keywords: BsAbs, MM, ...

2. ashpublications.org ashpublications.org/bloodict/article/1/1/100001/536578/Talquetamab-in-heavily-pretreated-patients-with

Talquetamab in heavily pretreated patients with multiple ... To our knowledge, this report is the first to illustrate the outcomes and safety profile of talquetamab in a real-world population of patients ...

3. thelancet.com thelancet.com/journals/lanhae/article/PIIS2352-3026(24)00385-5/fulltext

Safety and activity of talquetamab in patients with relapsed ... Talquetamab continued to demonstrate high overall response rates in heavily pretreated patients with relapsed or refractory multiple myeloma ...

4. ahdbonline.com ahdbonline.com/articles/ongoing-analyses-and-recent-data-for-talvey-in-multiple-myeloma

Ongoing Analyses and Recent Data for Talvey in Multiple ... Patients receiving talquetamab-tgvs with a median of 20 to 30 months of follow-up at either dose had an ORR of 74.1% (0.4-mg/kg weekly dose) and ...

5. jnj.com jnj.com/innovativemedicine/emea/newsroom/oncology/talvey-talquetamab-demonstrated-highly-durable-longer-term-responses-in-patients-with-relapsed-or-refractory-multiple-myeloma

TALVEY®▼ (talquetamab) demonstrated highly durable, ... 24-month overall survival rate of 67 percent achieved with talquetamab 0.8mg/kg biweekly dosing in the Phase 1/2 MonumenTAL-1 study1.

6. jnj.com jnj.com/media-center/press-releases/talvey-talquetamab-tgvs-demonstrates-highly-durable-longer-term-responses-in-patients-with-relapsed-or-refractory-multiple-myeloma

TALVEY® (talquetamab-tgvs) demonstrates highly durable, ... 24-month overall survival rate of 67 percent achieved with TALVEY® 0.8 mg/kg biweekly dosing in the Phase 1/2 MonumenTAL-1 study.