Talquetamab for Multiple Myeloma

(MonumenTAL-1 Trial)

Recruiting at 102 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Janssen Research & Development, LLC

Must not be taking: Corticosteroids

Disqualifiers: CAR-T therapy, Stroke, Seizure, others

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

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 2 years and 10 months

510 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called talquetamab (also known as Talvey) to determine its effectiveness and safety for people with multiple myeloma, a type of blood cancer, who haven't responded to other treatments. Participants will receive talquetamab in different groups based on their previous treatments. Those who have had multiple myeloma for a while and have tried at least three other treatments, including specific drugs or therapies, might be suitable for this trial. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to important medical advancements.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, it mentions that any side effects from previous cancer treatments should be resolved to a certain level before starting the study drug.

Is there any evidence suggesting that talquetamab is likely to be safe for humans?

Research has shown that talquetamab is well-tolerated by patients with relapsed or refractory multiple myeloma. Studies have demonstrated high response rates even in patients who had already received several treatments. The FDA granted talquetamab accelerated approval in August 2023 due to its promising safety and effectiveness.

In terms of safety, the treatment was tested in people with multiple myeloma who had undergone many previous therapies. Most patients tolerated talquetamab well, though some experienced side effects, such as cytokine release syndrome, where the immune system overreacts. This condition can be managed with tocilizumab. Thus, while potential side effects exist, they are known and manageable under medical supervision. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Talquetamab is unique because it targets a protein called GPRC5D, which is highly expressed on multiple myeloma cells but not on most normal cells. This is different from the standard treatments like proteasome inhibitors, immunomodulatory drugs, and CD38 monoclonal antibodies that target other pathways. By focusing on GPRC5D, talquetamab offers a novel mechanism of action that could potentially overcome resistance to existing therapies. Researchers are excited about this approach as it provides a fresh avenue for attacking the cancer cells while sparing healthy ones, potentially leading to more effective and safer treatment options for patients with multiple myeloma.

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

Studies have shown that talquetamab holds promise for treating multiple myeloma, particularly in patients who have tried other treatments. In one study, talquetamab helped shrink or eliminate cancer in 73% of patients. Another study found that about 85% of patients maintained their positive results for at least nine months. Talquetamab works by enabling the body's immune cells, called T-cells, to attack cancer cells. Early results suggest it can be effective even for those who have undergone many previous treatments. Participants in this trial will receive talquetamab in different cohorts, each designed to assess its effectiveness and safety in various patient populations. ^{1 2 4 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 adults with multiple myeloma that has come back or hasn't responded to treatment. They must be able to follow the study rules, have a certain level of physical ability (ECOG score 0-2), and women who can have children need a negative pregnancy test. People can't join if they've had a stroke or seizure recently, certain previous cancer treatments, unresolved side effects from past therapies (except hair loss or mild nerve pain), or recent high doses of steroids.

Inclusion Criteria

My multiple myeloma can be measured by tests.

Women who could become pregnant need to have a negative pregnancy test before starting the study.

Willing and able to adhere to the prohibitions and restrictions specified in this protocol

Exclusion Criteria

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

Side effects from my past cancer treatments have mostly gone away.

I have been treated with CAR-T or T cell therapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive talquetamab subcutaneously at a recommended Phase 2 dose, with biweekly dosing and tocilizumab prophylaxis for CRS in some cohorts

Up to 2 years and 10 months

Open-label extension (OLE)

Participants transition to OLE phase and continue to receive study treatment

Long-term extension (LTE)

Participants transition to LTE phase and continue to receive study treatment upon approval of amendment 19

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Talquetamab

Trial Overview The study is testing Talquetamab's effectiveness and safety in patients with relapsed/refractory multiple myeloma at recommended Phase 2 doses. Participants will receive this investigational drug to see how well it works against their cancer.

How Is the Trial Designed?

Group I: Part 3: Cohort E (Talquetamab) Experimental Treatment 1 Intervention

Cohort E will enroll participants with multiple myeloma who have previously received at least 1 proteasome inhibitor (PI), 1 immunomodulatory imide drug (IMiD), and 1 anti-cluster of differentiation 38 (CD38) monoclonal antibody. Participants will receive talquetamab SC biweekly at a RP2D selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study. Participants will receive tocilizumab prophylaxis for CRS with consolidated priming dose schedules as well as possible transition to outpatient priming dosing transition to OLE upon communication by the sponsor. Upon approval of amendment 19 and notification from the sponsor, participants will transition to the LTE and will continue to receive study treatment.

Group II: Part 3: Cohort D (Talquetamab) Experimental Treatment 1 Intervention

Cohort D will enroll participants with multiple myeloma who have previously received \>= 3 prior lines of therapy. Participants will receive talquetamab SC biweekly at a RP2D selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study. Participants in this cohort will receive tocilizumab prophylaxis for cytokine release syndrome (CRS) including all outpatient dosing. Participants will transition to OLE upon communication by the sponsor. Upon approval of amendment 19 and notification from the sponsor, participants will transition to the LTE and will continue to receive study treatment.

Group III: Part 3: Cohort C (Talquetamab) Experimental Treatment 1 Intervention

Cohort C will enroll participants with multiple myeloma who have previously received \>= 3 prior lines of therapy and have not been exposed to T cell redirection therapies. Participants will receive talquetamab SC biweekly at a RP2D selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study. All participants (ongoing and those who are in follow-up) will transition to OLE phase and will continue to receive the study treatment. Upon approval of amendment 19 and notification from the sponsor, participants will transition to the LTE and will continue to receive study treatment.

Group IV: Part 3: Cohort B (Talquetamab) Experimental Treatment 1 Intervention

Cohort B will enroll participants with multiple myeloma who have previously received \>= 3 prior lines of therapy and have been exposed to T cell redirection therapies. Participants will receive talquetamab subcutaneously (SC) at a recommended Phase 2 dose (RP2D) selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study. All participants (ongoing and those who are in follow-up) will transition to OLE phase and will continue to receive the study treatment. Upon approval of amendment 19 and notification from the sponsor, participants will transition to the LTE and will continue to receive study treatment.

Group V: Part 3: Cohort A (Talquetamab) Experimental Treatment 1 Intervention

Cohort A will enroll participants with multiple myeloma who have previously received greater than or equal to (\>=) 3 prior lines of therapy and have not been exposed to T cell redirection therapies. Participants will receive talquetamab subcutaneously (SC) at a recommended Phase 2 dose (RP2D) selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study. All participants (ongoing and those who are in follow-up) will transition to open-label extension (OLE) phase and will continue to receive the study treatment. Upon approval of amendment 19 and notification from the sponsor, participants will transition to the long-term extension (LTE) and will continue to receive study treatment.

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

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]

Monoclonal antibodies (MoAbs) like elotuzumab and daratumumab, which target specific antigens (CS1 and CD38) found in over 90% of multiple myeloma patients, show promising anti-myeloma effects, especially when combined with lenalidomide.

The article reviews various emerging MoAbs for multiple myeloma, highlighting their potential in improving treatment outcomes, although multiple myeloma remains largely incurable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic monoclonal antibodies against multiple myeloma]. Kuroda, J.[2019]

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]

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]

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]

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. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/7047/527044/Real-World-Outcomes-with-Talquetamab-a-T-Cell

Real World Outcomes with Talquetamab, a T-Cell-Redirecting ... The median PFS was 5.6 months, with 10 (37%) patients having relapsed and 17 (63%) pts continuing to have response on talquetamab. The mean OS ...

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

Talquetamab in Multiple Myeloma: Efficacy, Safety, and Future ... Novel bispecific antibodies (BsAbs), including talquetamab, have shown promising efficacy in heavily pretreated patients, even those with ...

3. talvey.com talvey.com/results-with-talvey/

Results with TALVEY® | TALVEY® (talquetamab-tgvs) Significant response rates in a clinical trial · An estimated 85% of people maintained their response for at least 9 months · More than half of the participants ...

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 ... 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 ...

5. 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 ...

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

Talquetamab in heavily pretreated patients with multiple ... Overall, the efficacy of talquetamab in our cohort was comparable with the results of the MonumenTAL-1 trial, with an ORR of ∼71%. In addition, ...