A study to evaluate preventive treatments for talquetamab-related oral toxicity
| ISRCTN | ISRCTN72589181 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN72589181 |
| IRAS number | 1009729 |
| ClinicalTrials.gov number | NCT06500884 |
| Secondary identifying numbers | 64407564MMY2006, IRAS 1009729, CPMS 61163 |
- Submission date
- 11/05/2024
- Registration date
- 14/08/2024
- Last edited
- 24/04/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Cancer
Plain English Summary
Background and study aims
Relapsed or refractory multiple myeloma (MM) is a blood cancer that forms in a type of white blood cells (WBCs) called plasma cells. Drugs that activate T-cells (type of WBCs) to attack cancer cells may be an effective way to destroy them. Cancer is called relapsed if it comes back after treatment and is called ‘refractory’ if does not respond to treatment. Talquetamab (JNJ-64407564) binds to proteins called cluster of differentiation 3 (CD3) receptor, found on T-cells and G protein-coupled receptor family C group 5 member D (GPRC5D), found on myeloma cells. This activates the T-cells and leads to the killing of myeloma cells. In this study, researchers want to learn how preventive measures started before the first dose of talquetamab & continued throughout the treatment phase, may reduce the number, intensity, or length of time for oral taste changes incidents related to talquetamab compared to no preventive measures for oral taste changes. This study is aimed to assess preventive measures for the side effects of an approved myeloma therapy (talquetamab).
Who can participate?
Male and female healthy participants 18 years or older with relapsed or refractory MM who have disease progression after receiving at least 1 of each of the following medication classes. PI, IMIDs, and anti-CD38 mAb.
What does the study involve?
The study will be conducted as:
1. Screening (Up to 28 days): Confirm if the participants can take part in the study.
2. Treatment Phase (Up to 12 months)*: Participants will be divided into either of the 4 treatment groups in a random way to receive the treatment:
• Cohort A (control): Talquetamab as an injection under the skin
• Cohort B: Prophylaxis mouth wash plus talquetamab
• Cohort C: Prophylaxis by mouth plus talquetamab
• Cohort D: Prophylaxis by mouth plus talquetamab
*Prophylaxis Treatment Phase duration could be longer than 12 months, if there are clinical benefits relevant to the participant and part of the objectives of the study, at treating physician’s discretion.
Talquetamab Treatment Phase: Until disease progression, death, talquetamab treatment discontinuation for any other reason (e.g. unacceptable toxicity, withdrawal of consent), or end of study, whichever occurs first.
3. Follow-up Phase (Up to approximately 12 months): Participants will be followed up for their overall health throughout the study.
During the study, some tests such as blood and urine tests, neurological examination, and physical examination will be performed. Side effects will be recorded until the study ends (Up to 12 to 30 months).
What are the possible benefits and risks of participating?
Taking talquetamab may or may not improve multiple myeloma. The benefit to study participants receiving talquetamab in this study cannot be guaranteed.
Participants may experience some benefit from participation in the study that is not due to receiving talquetamab but rather is due to regular visits and assessments monitoring overall health. Participation in the study may help other people with multiple myeloma in the future.
Participants may have side effects from the drug(s) or procedures used in this study that may be mild to severe and even life-threatening, and they can vary from person to person. The most common, known risks are getting symptoms such as cytokine release syndrome (CRS), cytopenias, skin and nail changes, oral side-effects, infection, injection-site reactions, and increased risk for immune effector cell-associated neurotoxicity syndrome (ICANS). The participant information sheet and informed consent form, which will be signed by every participant agreeing to participate in the study, includes a detailed section outlining the known risks of participating in the study. Not all possible side effects and risks related to talquetamab are known at this moment. During the study, the sponsor may learn new information about talquetamab. The study doctor will tell participants as soon as possible about any new information that might make them change their minds about being in the study, such as new risks.
To minimise the risk associated with taking part in the study, participants are frequently looked at and asked about any side effects and other medical events. Participants are educated to report any such events to the study doctor who will provide appropriate medical care. Any serious side effects that are reported to the sponsor are thoroughly reviewed by a safety team. There are no costs to participants to be in the study. The sponsor will pay for the study drug and tests that are part of the study. The participant will receive reasonable reimbursement for study-related costs (for example, travel/parking costs).
Where is the study run from?
Janssen-Cilag International NV
When is the study starting and how long is it expected to run for?
May 2024 to January 2027 (recruitment will start August 2024)
Who is funding the study?
Janssen-Cilag International NV
Who is the main contact?
JanssenUKRegistryQueries@its.jnj.com
Contact information
Scientific
50-100 Holmers Farm Way
High Wycombe
HP12 4DP
United Kingdom
| Phone | +44 (0)7785380332 |
|---|---|
| JanssenUKRegistryQueries@its.jnj.com |
Principal Investigator
University College London Hospitals NHS Foundation Trust (UCLH)
3rd floor west, 250 Euston Road
London
NW1 2BU
United Kingdom
Study information
| Study design | Multi-centre randomized controlled open-label parallel-group study |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Safety, Efficacy |
| Participant information sheet | Not available in web format, please use contact details to request a participant information sheet |
| Scientific title | A phase II, open-label, randomized study to evaluate prophylactic interventions on talquetamab-related oral toxicity |
| Study acronym | TALISMAN |
| Study hypothesis | Primary objectives: 1. To find preventive measures that can reduce number, intensity, and length of time for taste change incidents related to talquetamab during treatment phase. 2. To better understand the signs and symptoms of taste changes related to talquetamab. Secondary objectives: 1. To find out the impact of preventive measures on problems with sense of taste. 2. To assess harmful effects in the mouth due to treatment-related side effects. 3. To assess quality of life parameters related to overall health and specific impact of taste changes, xerostomia (dry mouth), dysphagia (difficulty swallowing), oral mucositis (mouth ulcers), and other harmful effects in mouth. 4. To assess the impact of preventive measures on change in body weight. 5. To assess participants’ ability to follow the talquetamab treatment schedule. 6. To assess the impact of preventive measures on smell function. 7. To determine how well (efficacy) talquetamab works. 8. To determine safety of talquetamab and preventive measures. |
| Ethics approval(s) |
Approved 01/08/2024, North East - Tyne & Wear South Research Ethics Committee (NHSBT Newcastle Blood Donor Centre, Holland Drive, Newcastle upon Tyne, NE2 4NQ, United Kingdom; +44 (0)20 710 48120; tyneandwearsouth.rec@hra.nhs.uk), ref: 24/NE/0099 |
| Condition | Multiple myeloma |
| Intervention | Cohort A: Talquetamab. Participants with relapsed or refractory multiple myeloma (RRMM) (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 progressive disease, death, lost to follow-up, withdrawal of consent, discontinuation because of toxicity, or until 12 months after the start of talquetamab treatment, whichever occurs first. Cohort B: Prophylaxis A and Talquetamab. Participants with RRMM (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 1 week before starting talquetamab treatment. After step-up dosing of talquetamab therapy, participants will be treated with talquetamab until progressive disease, death, lost to follow-up, withdrawal of consent, discontinuation because of toxicity, or until 12 months after the start of talquetamab treatment, whichever occurs first. Cohort C: Prophylaxis B and Talquetamab. Participants with RRMM (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 1 week before starting talquetamab treatment. After step-up dosing of talquetamab therapy, participants will be treated with talquetamab until progressive disease, death, lost to follow-up, withdrawal of consent, discontinuation because of toxicity, or until 12 months after the start of talquetamab treatment, whichever occurs first. Cohort D: Prophylaxis C and Talquetamab. Participants with RRMM (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 1 week before starting talquetamab treatment. After step-up dosing of talquetamab therapy, participants will be treated with talquetamab until progressive disease, death, lost to follow-up, withdrawal of consent, discontinuation because of toxicity, or until 12 months after the start of talquetamab treatment, whichever occurs first. |
| Intervention type | Drug |
| Pharmaceutical study type(s) | Pharmacokinetic, Prophylaxis, Others (Oral toxicity, immunogenicity, biomarkers) |
| Phase | Phase II |
| Drug / device / biological / vaccine name(s) | Talquetamab, prophylaxis A, prophylaxis B, prophylaxis C |
| Primary outcome measure | 1. Percentage of participants with the occurrence of taste dysfunction (hypogeusia) measured using the Total Waterless Empirical Taste Test (WETT) score up to 12 months 2. Percentage of participants with the occurrence of severe hypogeusia measured using the WETT score up to 12 months 3. Time to first onset of severe hypogeusia measured using the WETT score up to 12 months 4. Percentage of participants who report resolution/improvement of hypogeusia/ageusia measured using the WETT score at months 3 and 6 |
| Secondary outcome measures | 1. Change from baseline in WETT testing score over time up to 30 months 2. Percentage of time with hypogeusia up to 12 months 3. Number of participants with treatment-emergent oral toxicities (dysgeusia, oral mucositis, dysphagia, and xerostomia) up to 30 months 4. Time to the first onset of treatment-emergent oral toxicities (dysgeusia, oral mucositis, dysphagia, and xerostomia) up to 30 months 5. Duration of treatment-emergent oral toxicities (dysgeusia, oral mucositis, dysphagia, and xerostomia) up to 30 months 6. Change from baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 items (EORTC-QLQ-C30) domains scores up to 30 months 7. Change from baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Oral Health (EORTC-QLQ-OH15) domains scores up to 30 months 8. Percentage of participants reporting oral toxicity symptoms using the Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) up to 12 months 9. Percentage of participants reporting oral toxicity symptoms using the Short Xerostomia Inventory (SXI) score up to 30 months 10. Percentage of participants reporting oral toxicity symptoms using the Epstein Taste Survey (ETS) up to 30 months 11. Percentage of participants reporting oral toxicity symptoms using the Scale of Subjective Total Taste Acuity (STTA) up to 12 months 12. Change from baseline in body weight over time up to 30 months 13. Change from baseline in Body Mass Index (BMI) over time up to 30 months 14. Percentage of participants with dose reductions, interruptions, and discontinuations up to 12 months 15. Change from baseline in Smell Identification Test Score at day 1 cycles 1, 4, 8 and 12 16. Change from baseline in Smell Detection Threshold Test Score at day 1 cycles 1, 4, 8 and 12 17. Percentage of participants with Overall Response Rate up to 30 months 18. Percentage of participants with Complete Response (CR) or Better Response up to 30 months 19. Percentage of participants with Very Good Partial Response (VGPR) or Better Response up to 30 months 20. Duration of Response (DOR) up to 30 months 21. Time to Response (TTR) up to 30 months 22. Number of participants with Treatment-emergent Adverse Events (TEAEs) up to 30 months |
| Overall study start date | 08/05/2024 |
| Overall study end date | 18/10/2027 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | 120 |
| Participant inclusion criteria | 1. Multiple myeloma (MM) according to IMWG diagnostic criteria 2. Were triple-class exposed (received prior treatment with a PI, an IMiD, and anti-CD38 mAb) 3. Documented evidence of progressive disease based on the investigator’s determination of response by IMWG criteria on or after their last regimen 4. Have an Eastern Cooperative Oncology Group performance status (ECOG-PS) of 0 or 1 at screening. Participants with ECOG PS 2 or 3 are eligible for the study if the ECOG-PS score is related to stable physical limitations (e.g., wheelchair-bound due to prior spinal cord injury) and not related to multiple myeloma or associated therapy 5. Be willing and able to adhere to the lifestyle restrictions specified in the protocol |
| Participant exclusion criteria | 1. Contraindications or life-threatening known allergies, hypersensitivity, or intolerance to any study drug or its excipients 2. Stroke, transient ischemic attack, or seizure within 6 months prior to enrollment 3. Any of the following within 6 months prior to the first dose of study treatment: severe or unstable angina, myocardial infarction; major thromboembolytic event (e.g., pulmonary embolism, cerebrovascular accident), clinically significant ventricular arrythmia or heart failure New York Heart Association functional classification Class III or IV. Uncomplicated deep vein thrombosis is not considered exclusionary 4. Major surgery or had significant traumatic injury within 2 weeks prior to the start of administration of study treatment, or will not have fully recovered from surgery, or has major surgery planned during the time the participant is expected to be treated in the study or within 2 weeks after administration of the last dose of study treatment 5. A WETT score suggesting severe hypogeusia or ageusia at screening. Also, unresolved/severe dysgeusia referred by the participant or a finding in the physical examination/oral cavity inspection. Some examples include leukoplakia, prior mouth cancers, extensive dental caries, severe periodontitis, active oral infections, candidiasis, parotic gland removal, or radiotherapy with resultant xerostomia |
| Recruitment start date | 16/04/2025 |
| Recruitment end date | 17/10/2026 |
Locations
Countries of recruitment
- Brazil
- England
- Korea, South
- Netherlands
- Northern Ireland
- Spain
- United Kingdom
- United States of America
Study participating centres
London
NW1 2BU
United Kingdom
Hammersmith
London
W12 0HS
United Kingdom
Liverpool
L7 8YA
United Kingdom
Belfast
BT9 7AB
United Kingdom
High Heaton
Newcastle upon Tyne
NE7 7DN
United Kingdom
Turner Road
Colchester
CO4 5JL
United Kingdom
Sao Paulo
04501-000
Brazil
Amsterdam
1081 HV
Netherlands
Seoul
110-460
Korea, South
Madrid
28041
Spain
New York
10029
United States of America
Withington
Manchester
M20 4BX
United Kingdom
Sponsor information
Industry
Archimedesweg 29
Leiden
2333 CM
Netherlands
| Phone | +31 71 524 21 06 |
|---|---|
| ClinicalTrialsEU@its.jnj.com | |
| Website | https://www.janssen.com/ |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 15/01/2028 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in non-publicly available repository, Available on request |
| Publication and dissemination plan | 1. Peer reviewed scientific journals 2. Internal report 3. Conference presentation 4. Publication on website 5. Submission to regulatory authorities The results of the study will be available to the wider scientific community via publication in scientific journals and presentation at scientific meetings. Study results will be available to participants via the provision of a Plain Language Summary at the end of the study. |
| IPD sharing plan | The Janssen Pharmaceutical Companies of Johnson & Johnson data sharing policy is available at www.janssen.com/clinicaltrials/transparency. As noted on this site, requests for access to the study data can be submitted through the Yale Open Data Access (YODA) Project site at https://yoda.yale.edu/. |
Editorial Notes
24/04/2025: The following changes were made to the trial record:
1. The recruitment start date was changed from 23/08/2024 to 16/04/2025.
2. The recruitment end date was changed from 15/01/2026 to 17/10/2026.
3. The overall end date was changed from 15/01/2027 to 18/10/2027.
4. The study participating centre The Christie was added.
5. The plain English summary was updated to reflect these changes.
30/10/2024: A global recruitment halt was enforced on 17/09/2024 so that additional dose strengths could be sourced before any participants were recruited in the UK.
13/05/2024: Study's existence confirmed by Health Research Authority (HRA) (UK).
