Talquetamab for Multiple Myeloma

(MonumenTAL-1 Trial)

Recruiting at 91 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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to evaluate the efficacy and safety of talquetamab in participants with relapsed or refractory multiple myeloma at the recommended Phase 2 dose(s) (RP2Ds) (Part 3).

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.

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 from Talquetamab, a drug that 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 tested in early clinical trials for multiple myeloma, showing it is generally well-tolerated with some side effects like skin, mouth, and nail issues. It has fewer infections compared to similar treatments, indicating a favorable safety profile. ^{1 2 3 4 5}

How is the drug Talquetamab different from other treatments for 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. ^{1 2 3 4 6}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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 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]

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]

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]

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]

References

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

Talquetamab: First Approval. [2023]

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

MonumenTAL Results for Talquetamab in Myeloma. [2023]

3. Italy pubmed.ncbi.nlm.nih.gov

Talquetamab in multiple myeloma. [2023]

4. 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]

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

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

6. Japan pubmed.ncbi.nlm.nih.gov

[Therapeutic monoclonal antibodies against multiple myeloma]. [2019]