Preventive Treatments for Talquetamab-Related Oral Toxicity in Multiple Myeloma

(Talisman Trial)

Recruiting at 43 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Janssen Research & Development, LLC

Disqualifiers: Stroke, Seizure, Heart failure, 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

130 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to identify preventive treatments that can reduce taste changes caused by talquetamab (Talvey), a drug used for multiple myeloma, a type of blood cancer. Researchers seek to determine how different preventive approaches can minimize taste issues and improve patients' experiences. Participants will join different groups to receive talquetamab alone or with various preventive measures. Individuals previously treated with certain myeloma drugs and experiencing disease progression might be suitable for this study. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Do I have to stop taking my current medications for this trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you should discuss your current medications with the trial team to ensure they don't interfere with the study.

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

Research has shown that talquetamab has been tested in patients with multiple myeloma, revealing some side effects. These include cytokine release syndrome (CRS), which can cause fever, nausea, and tiredness, as well as infections and changes in taste. Some patients also experienced nervous system effects and a drop in white blood cells, increasing infection risk.

In a study involving 339 patients, these side effects appeared, with some serious enough to require hospital care, particularly for CRS and nervous system effects. However, many patients managed these side effects with medical assistance.

While talquetamab has shown promise in treating relapsed or hard-to-treat multiple myeloma, potential participants should consider these safety findings. These studies help doctors understand how well patients tolerate the treatment and what side effects might occur. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about talquetamab for multiple myeloma because it offers a unique approach compared to existing treatments like proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies. Talquetamab is a bispecific antibody that targets both the GPRC5D protein on myeloma cells and the CD3 protein on T-cells, effectively directing the immune system to attack the cancer cells. This dual-targeting mechanism sets it apart from the current standard of care by potentially enhancing the body's natural immune response against the disease. Additionally, talquetamab is administered subcutaneously, which may offer a more convenient and less invasive option compared to intravenous infusions, improving patient comfort and compliance.

What evidence suggests that this trial's treatments could be effective for talquetamab-related oral toxicity in multiple myeloma?

Research has shown that talquetamab holds promise for treating relapsed or refractory multiple myeloma, a type of blood cancer. Studies have found that it has a high overall response rate, meaning the cancer shrinks or stops growing in many patients. In this trial, participants in Cohort A will receive talquetamab alone, while Cohorts B, C, and D will receive talquetamab with different prophylaxis treatments to prevent oral toxicity. Talquetamab also appears effective over long periods, and most patients tolerate it well. These results suggest talquetamab could be a good option for those who haven't had success with other treatments. ^{1 6 7 8 9}

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 individuals with multiple myeloma who have seen their disease progress after treatment. They should be relatively active (able to care for themselves or up and about more than half of the day) and able to follow certain lifestyle restrictions. Those who've had prior treatments with proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies can join.

Inclusion Criteria

My cancer has worsened after my last treatment, as confirmed by my doctor.

I have been diagnosed with multiple myeloma.

I have been treated with proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Prophylaxis Treatment

Participants receive prophylactic interventions to minimize talquetamab-related oral toxicity, starting 7 days before talquetamab treatment

Up to 12 months

Talquetamab Treatment

Participants are treated with talquetamab subcutaneously until disease progression, death, unacceptable toxicity, withdrawal of consent, or end of study

Up to 30 months

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 aims to find out which preventive treatments are best at reducing taste distortion caused by talquetamab in patients with multiple myeloma. Participants will receive one of three prophylactic treatments alongside talquetamab to see which is most effective.

How Is the Trial Designed?

Group I: Cohort D: Prophylaxis C and Talquetamab Experimental Treatment 2 Interventions

Participants with RRMM who are triple-class exposed (previously exposed to at least 1 PI, 1 IMiD, and an anti-CD38 mAb) will receive prophylaxis C along with talquetamab therapy. Participants will start the assigned prophylaxis 7 days before starting talquetamab treatment. After step-up dosing of talquetamab therapy, participants will be treated with talquetamab with prophylaxes for up to 12 months during prophylaxis treatment phase (if there are clinical benefits prophylaxis treatment can continue beyond 12 months, at the treating physician's discretion, after consultation with sponsor). The Talquetamab treatment phase will continue from C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent, discontinuation of talquetamab, or end of study, whichever occurs first.

Group II: Cohort C: Prophylaxis B and Talquetamab Experimental Treatment 2 Interventions

Participants with RRMM who are triple-class exposed (previously exposed to at least 1 PI, 1 IMiD, and an anti-CD38 mAb) will receive prophylaxis B along with talquetamab therapy. Participants will start the assigned prophylaxis 7 days before starting talquetamab treatment. After step-up dosing of talquetamab therapy, participants will be treated with talquetamab with prophylaxes for up to 12 months during prophylaxis treatment phase (if there are clinical benefits prophylaxis treatment can continue beyond 12 months, at the treating physician's discretion, after consultation with sponsor). The Talquetamab treatment phase will continue from C1D1 until disease progression, death, unacceptable toxicity, withdrawal of consent, discontinuation of talquetamab, or end of study, whichever occurs first.

Group III: Cohort B: Prophylaxis A and Talquetamab Experimental Treatment 2 Interventions

Participants with RRMM who are triple-class exposed (previously exposed to at least 1 PI, 1 IMiD, and an anti-CD38 mAb) will receive prophylaxis A along with talquetamab therapy. Participants will start the assigned prophylaxis 7 days before starting talquetamab treatment. After step-up dosing of talquetamab therapy, participants will be treated with talquetamab with prophylaxes for up to 12 months during prophylaxis treatment phase (if there are clinical benefits prophylaxis treatment can continue beyond 12 months, at the treating physician's discretion, after consultation with sponsor). The Talquetamab treatment phase will continue from Cycle 1 Day 1 (C1D1) until disease progression, death, unacceptable toxicity, withdrawal of consent, discontinuation of talquetamab, or end of study, whichever occurs first.

Group IV: Cohort A: Talquetamab Active Control 1 Intervention

Participants with relapsed or refractory multiple myeloma (RRMM) who are triple-class exposed (previously exposed to at least 1 proteasome inhibitor \[PI\], 1 immunomodulatory drug(s) \[IMiD\]), and an anti-CD38 monoclonal antibody \[mAb\]) will be treated with talquetamab subcutaneously until disease progression, death, unacceptable toxicity, withdrawal of consent, discontinuation of talquetamab, or end of study, whichever occurs first.

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 novel bispecific antibody for treating multiple myeloma, caused significant taste changes and dry mouth in patients, with 60% experiencing dysgeusia and 30-57% reporting xerostomia shortly after treatment began.

In a study of eight heavily pretreated multiple myeloma patients, talquetamab led to a marked decrease in taste scores and a significant decline in quality of life related to oral health, despite no changes in salivary flow, highlighting the need to understand these oral toxicities better.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterization of dysgeusia and xerostomia in patients with multiple myeloma treated with the T-cell redirecting GPRC5D bispecific antibody talquetamab. Laheij, AMGA., van de Donk, NWCJ.[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]

Long-term continuous treatment for multiple myeloma (MM) is crucial for improving patient survival, but the burden of treatment can negatively affect quality of life.

Common side effects of oral MM therapies include blood-related issues like thrombocytopenia, gastrointestinal problems, and venous thrombotic events, highlighting the need for proactive symptom management and support for patients to enhance treatment sustainability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating Multiple Myeloma Patients With Oral Therapies. Kumar, SK., Vij, R., Noga, SJ., et al.[2022]

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]

Belantamab mafodotin is a newly approved treatment for relapsed or refractory multiple myeloma, showing an overall response rate of 31% and a median progression-free survival of 2.9 months in patients who have undergone at least four prior therapies.

While the treatment is generally well tolerated, it is associated with notable ocular toxicities, which require careful management during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of Ocular Toxicity in Patients Receiving Belantamab Mafodotin. Lu, R., Morphey, A., Diaz, F., et al.[2023]

Citations

1.

pmc.ncbi.nlm.nih.gov

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

Talquetamab in Multiple Myeloma: Efficacy, Safety, and Future ...

The efficacy data showed were overlapping for both dose levels. Efficacy outcomes, assessed according to International Myeloma Working Group ( ...

2.

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 ...

In summary, we found that talquetamab exhibited a comparable efficacy and safety profile in the real-world setting as in the pivotal trial.

3.

hematologyadvisor.com

hematologyadvisor.com/news/multiple-myeloma-monumental1-talquetamab-durable-response-treatment-risk/

Talquetamab Shows Durable Responses, Tolerable Safety ...

The investigators concluded that talquetamab treatment in patients with RRMM continues to show high ORRs even at a longer follow-up period of 36 ...

4.

targetedonc.com

targetedonc.com/view/talquetamab-combo-yields-high-responses-in-heavily-pretreated-myeloma

Talquetamab Combo Yields High Responses in Heavily ...

Talquetamab and daratumumab combination achieved an 82.4% overall response rate in relapsed/refractory multiple myeloma patients, with a median ...

5.

talvey.com

talvey.com/results-with-talvey/

Results with TALVEY® | TALVEY® (talquetamab-tgvs)

TALVEY was studied in 219 people with relapsed or refractory multiple myeloma who had previously been on at least 4 prior lines of therapy.

6.

accessdata.fda.gov

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

Talvey - accessdata.fda.gov

Due to the risk of CRS and neurologic toxicity, including ICANS, patients should be hospitalized for 48 hours after administration of all doses within the ...

7.

ema.europa.eu

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

Talvey, INN-talquetamab - European Medicines Agency

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

8.

talveyhcp.com

talveyhcp.com/pdfs/TALVEY_Treatment_Mgmt_Guide.pdf

TALVEY® TREATMENT MANAGEMENT GUIDE

TALVEY® (talquetamab-tgvs) is indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior ...

9.

clinicaltrials.gov

clinicaltrials.gov/study/NCT06500884

NCT06500884 | A Study to Evaluate Preventive Treatments ...

The purpose of this study is to identify preventive treatments that can minimize the occurrence, severity, and duration of talquetamab-related taste changes ...