Talquetamab for Multiple Myeloma

(MonumenTAL-1 Trial)

Not currently recruiting at 19 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Janssen Research & Development, LLC

Must not be taking: Live vaccines, Corticosteroids

Disqualifiers: Recent stem cell transplant, CNS involvement, 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Talquetamab for multiple myeloma, a type of blood cancer. Researchers aim to determine Talquetamab's safety and identify the best dose for future studies. Participants will receive the treatment through an IV or injection, and the trial will explore different doses to find the most effective one. It suits individuals whose multiple myeloma does not respond to other treatments or who cannot tolerate them. As a Phase 1 trial, this research focuses on understanding how Talquetamab works in people, offering participants the opportunity 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. 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.

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

Research shows that Talquetamab has been tested in patients with multiple myeloma, a type of blood cancer. Talquetamab, administered through an IV (intravenous) or as a shot under the skin (subcutaneous), has a safety profile similar to other treatments. Common side effects include blood cell issues, such as anemia (low red blood cells) and neutropenia (low white blood cells).

However, there are serious risks. Talquetamab can cause severe brain and nervous system problems, including immune effector cell-associated neurotoxicity syndrome. The subcutaneous form may also trigger cytokine release syndrome, a strong immune reaction.

The FDA has approved the treatment for patients with advanced, previously treated multiple myeloma, indicating thorough safety testing in that context. Nonetheless, potential risks should be considered when deciding to join a clinical trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for multiple myeloma, which often include chemotherapy, proteasome inhibitors, and immunomodulatory drugs, Talquetamab is unique because it is an antibody that targets a specific protein called GPRC5D on multiple myeloma cells. This new mechanism of action could provide a targeted approach to attacking cancer cells without harming normal cells, potentially reducing side effects. Researchers are excited about Talquetamab because it offers a fresh strategy for treating multiple myeloma, which could improve outcomes for patients who have not responded well to existing therapies. Additionally, it can be administered both intravenously and subcutaneously, providing more flexibility in how it is delivered to patients.

What evidence suggests that Talquetamab might be an effective treatment for multiple myeloma?

Research shows that talquetamab has promising results for treating multiple myeloma, a type of blood cancer. Studies found that 73% of patients responded positively to the treatment, meaning their cancer improved. In some trials, 63% of patients continued to benefit from talquetamab, with more than half maintaining improvement for over nine months. Even patients with many previous treatments found talquetamab effective. These findings suggest talquetamab could be a strong option for people with multiple myeloma. Participants in this trial will receive talquetamab through either intravenous (IV) infusion or subcutaneous (SC) injection during the dose escalation or dose expansion phases. ^{1 3 6 7 8}

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'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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Talquetamab

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.

How Is the Trial Designed?

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.

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]

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]

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]

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]

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. talveyhcp.com talveyhcp.com/safety/

Side Effects & Safety Profile | TALVEY® (talquetamab-tgvs) HCP TALVEY can cause serious, life-threatening neurologic toxicity or fatal neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome ( ...

7. ema.europa.eu ema.europa.eu/en/documents/product-information/talvey-epar-product-information_en.pdf

Talvey, INN-talquetamab - EMA The safety of TALVEY was evaluated in 339 adult patients with relapsed or refractory multiple myeloma, including patients treated with TALVEY at ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/761342s000lbl.pdf

Talvey - accessdata.fda.gov TALVEY is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, ...