Preventive Treatments for Talquetamab-Related Oral Toxicity in Multiple Myeloma

(Talisman Trial)

Recruiting at 19 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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to identify preventive treatments that can minimize the occurrence, severity, and duration of talquetamab-related taste changes (dysgeusia), during the prophylaxis (preventive) treatment phase, and to better characterize the signs or symptoms of talquetamab-related taste changes.

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.

What data supports the idea that Preventive Treatments for Talquetamab-Related Oral Toxicity in Multiple Myeloma is an effective drug?

The available research shows that nearly three quarters of the 288 patients with relapsed or refractory multiple myeloma in the MonumenTAL-1 trial experienced significant anticancer effects from talquetamab. This suggests that talquetamab is effective in treating this condition. Additionally, talquetamab has been granted accelerated approval in the USA and conditional marketing authorization in the EU for treating adults with relapsed or refractory multiple myeloma, indicating its recognized effectiveness. Compared to another treatment, belantamab mafodotin, which had a response rate of 31% and a median progression-free survival of 2.9 months, talquetamab shows a higher rate of significant anticancer effects. ^{1 2 3 4 5}

What safety data is available for Talquetamab in treating multiple myeloma?

Talquetamab, also known as Talvey, has been evaluated for safety in multiple studies. It was granted accelerated approval in the USA and conditional marketing authorization in the EU for relapsed or refractory multiple myeloma. In clinical trials, Talquetamab showed significant anticancer effects but also presented unique side effects, including dysgeusia (taste changes) in 60% of patients and xerostomia (dry mouth) in 30-57% of patients. It has fewer infections compared to teclistamab but includes skin, oral, and nail-related adverse events. Despite these side effects, it is considered a well-tolerated and effective treatment option for heavily pretreated multiple myeloma. ^{1 2 3 4 6}

Is the drug Talquetamab a promising treatment for multiple myeloma?

Yes, Talquetamab is a promising drug for multiple myeloma. It has shown significant anticancer effects in nearly three-quarters of patients in trials and has been approved for use in the USA and EU for patients with relapsed or refractory multiple myeloma. ^{1 2 3 4 5}

Research Team

Janssen Research & Development, LLC Clinical Trial

Principal Investigator

Janssen Research & Development, LLC

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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 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 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]

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]

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]

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 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]

References

1. Germany 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. [2023]

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

Talquetamab: First Approval. [2023]

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

Management of Ocular Toxicity in Patients Receiving Belantamab Mafodotin. [2023]

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

MonumenTAL Results for Talquetamab in Myeloma. [2023]

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

Treating Multiple Myeloma Patients With Oral Therapies. [2022]

6. Italy pubmed.ncbi.nlm.nih.gov

Talquetamab in multiple myeloma. [2023]