Talquetamab for Multiple Myeloma

(MonumenTAL-1 Trial)

Recruiting at18 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Janssen Research & Development, LLC

Must not be taking: Live vaccines, Corticosteroids

Disqualifiers: Recent stem cell transplant, CNS involvement, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests Talquetamab, a new drug, in adults with multiple myeloma that has come back or didn't respond to other treatments. Doctors will monitor patients' health to see if the drug works and is safe.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that any toxicities from previous cancer treatments should have resolved to baseline levels or to a mild 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}

What makes the drug Talquetamab unique for treating multiple myeloma?

Talquetamab is unique because it is a first-in-class bispecific antibody that targets GPRC5D, a protein 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 5 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's gotten worse after standard treatments or who couldn't handle those treatments. They must understand the study and agree to participate, have a good performance status (able to carry out daily activities), and meet specific disease measurement criteria. Women able to have children need a negative pregnancy test.

Inclusion Criteria

Sign an informed consent form (ICF) indicating that he or she understands the purpose of and procedures required for the study, and is willing to and able participate in the study. Consent is to be obtained prior to the initiation of any study-related tests or procedures that are not part of standard-of-care for the participant's disease

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

I am fully active or can carry out light work.

Exclusion Criteria

I have taken a lot of steroids, like prednisone, recently.

I haven't had any live vaccines recently and won't until after the trial.

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

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive Talquetamab via IV or SC to determine the recommended Phase 2 dose(s) (RP2Ds)

Up to 4 weeks

Dose Expansion

Further characterization of the safety of Talquetamab at the recommended Phase 2 dose(s) (RP2Ds)

Approximately 2.10 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

100 days after the last dose

Open-label extension (OLE)

Participants continue to receive the study treatment in an open-label extension phase

Long-term extension (LTE)

Participants transition to long-term extension and continue to receive study treatment

Treatment Details

Interventions

• Talquetamab (Monoclonal Antibodies)

Trial Overview The trial is testing Talquetamab, aiming to find the safest dose for Phase 2 trials. It has two parts: first, increasing doses to find what's safe (Dose Escalation), then giving this safe dose to more people (Dose Expansion) to confirm its safety.

Participant Groups

Group I: Part 2: Dose Expansion (Talquetamab) Experimental Treatment 1 Intervention

Participants will receive IV infusion or SC injection of Talquetamab at each putative recommended Phase 2 dose(s) (RP2D\[s\]) as determined in Part 1. Participants receiving IV dosing can transition to SC dosing through-out the study upon sponsor consultation. 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 II: Part 1: Dose Escalation (Talquetamab) - Subcutaneous (SC) Experimental Treatment 1 Intervention

Participants will receive Talquetamab SC. The dose levels will be selected to identify safe and tolerable putative RP2D(s). 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 III: Part 1: Dose Escalation (Talquetamab) - Intravenous (IV) Experimental Treatment 1 Intervention

Participants will receive IV infusion of Talquetamab at minimum anticipated biologic effect level (MABEL)-based starting dose until the completion of the end of treatment visit. Subsequent dose levels will be selected based on the review of all available data including, but not limited to, pharmacokinetic, pharmacodynamic, safety, and preliminary antitumor activity data. Participants receiving IV dosing can transition to SC dosing through-out the study upon sponsor consultation. 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.

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]

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]

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]

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. 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]

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

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

5. Italy pubmed.ncbi.nlm.nih.gov

Talquetamab in multiple myeloma. [2023]

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

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