Talquetamab Combinations for Multiple Myeloma

(MonumenTAL-6 Trial)

Recruiting at 297 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of different treatment combinations for multiple myeloma, a type of blood cancer. Researchers are comparing two experimental combinations: talquetamab (Talvey) with pomalidomide and talquetamab with teclistamab (Tecvayli), against existing treatments. This study targets individuals whose multiple myeloma has returned or has not responded well to previous treatments. Participants should exhibit noticeable symptoms or lab results indicating active disease. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants access to potentially groundbreaking 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.

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

Research shows that using talquetamab with teclistamab is about as safe as using each drug alone, with side effects aligning with those expected from past experiences with each treatment. Studies have found that talquetamab alone can lead to strong and lasting improvements in patients with serious multiple myeloma and is generally well-tolerated.

When combined with pomalidomide, research indicates that talquetamab's side effects remain manageable, even for high-risk patients, allowing them to handle the side effects without significant trouble. The FDA has already approved talquetamab for patients who have tried several other treatments, suggesting its safety is well-understood.

Overall, previous research indicates that both combinations appear safe. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the new combinations for multiple myeloma involving talquetamab because they offer fresh approaches to treatment. Talquetamab is unique since it targets the GPRC5D protein on myeloma cells, different from standard treatments that often target CD38 or SLAMF7. In the Tal-Tec combination, teclistamab adds another layer of action by targeting the BCMA protein, potentially enhancing the overall effectiveness. Meanwhile, the Tal-P combination offers a novel approach by pairing talquetamab with pomalidomide, which modulates the immune system differently than traditional therapies. These innovative mechanisms provide hope for improved outcomes in a disease where treatment options are constantly evolving.

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

Research has shown promising results for the treatments tested in this study. Participants may receive a combination of talquetamab and teclistamab, which studies report has an overall response rate (ORR) of up to 78.9%, with many patients experiencing complete recovery. This indicates significant improvements in their condition. Another group will receive talquetamab and pomalidomide, which has shown an ORR as high as 82% in some studies, indicating effective management of multiple myeloma. These findings suggest both treatment combinations have strong potential in treating relapsed or hard-to-treat multiple myeloma, with many patients responding well. ^{1 3 4 6 7}

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 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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

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 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]

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-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 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]

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]

Citations

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

Talquetamab in Multiple Myeloma: Efficacy, Safety, and Future ... Administered following a step‐up dosing phase to manage cytokine release syndrome (CRS), talquetamab demonstrated a high overall response rate ( ...

2. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/1014/501614/Talquetamab-Pomalidomide-in-Patients-with-Relapsed

Talquetamab + Pomalidomide in Patients with Relapsed ... Talquetamab + Pomalidomide in Patients with Relapsed/Refractory Multiple Myeloma: Safety and Preliminary Efficacy Results from the Phase 1b MonumenTAL-2 Study

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

Ongoing Analyses and Recent Data for Talvey in Multiple ... MonumenTAL-1 (NCT03399799/NCT04634552) was a phase 1/2 study that had shown a 73% overall response rate (ORR) in 100 patients receiving a 0.4-mg ...

4. 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.

5. cancernetwork.com cancernetwork.com/view/talquetamab-daratumumab-shows-durable-responses-in-r-r-multiple-myeloma

Talquetamab/Daratumumab Shows Durable Responses in ... An overall response rate (ORR) of 82% was observed in patients who received talquetamab plus daratumumab and pomalidomide, supporting the ...

6. 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 ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123076176

Talquetamab + Pomalidomide in Patients with Relapsed ... Tal has demonstrated deep and durable responses, including in high-risk populations, and a clinically manageable safety profile in patients (pts) with relapsed ...