A Study to Evaluate Preventive Treatments for GPRC5D-related Oral Events

Phase 2RecruitingNCT06500884

Janssen Research & Development, LLC210 enrolled

Overview

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, to better characterize the signs or symptoms of talquetamab-related taste changes and to better characterize the signs or symptoms of ramantamig-related taste changes.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

210

Conditions

Multiple Myeloma

Interventions

TalquetamabDRUG

Talquetamab will be administered subcutaneously.

Prophylaxis ADRUG

Prophylaxis A will be administered orally.

Prophylaxis BDRUG

Prophylaxis B will be administered orally.

Prophylaxis C

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Multiple myeloma (MM) according to IMWG diagnostic criteria * Were triple-class exposed (received prior treatment with a PI, an IMiD, and anti CD38 mAb) * Documented evidence of progressive disease based on investigator's determination of response by IMWG criteria on or after their last regimen * 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 * Be willing and able to adhere to the lifestyle restrictions specified in the protocol Exclusion Criteria: * Contraindications or life-threatening known allergies, hypersensitivity, or intolerance to any study drug or its excipients * Stroke, transient ischemic attack, or seizure within 6 months prior to screening * 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 * 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 * A WETT score indicating severe dysgeusia at screening and confirmed prior to randomization. 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

Locations (38)

Outcomes

Primary Outcomes

Percentage of Participants With Occurrence of Dysgeusia as Assessed by the Total Waterless Empirical Taste Test (WETT) Testing Score During the Prophylaxis Treatment Phase

Dysgeusia is defined as total WETT score of 25th percentile or below according to the Normative WETT-SA53 percentile table. Taste assessment will be performed using taste strips (WETT). Four concentrations (4=lowest concentration, 1=highest concentration) will be used for each taste quality: sweet, sour, salty, bitter, and umami. Each test kit contains 53 taste strips distributed in 4 packs; and each taste strip is numbered (1 through 53). Participants will use each strip sequentially and record the flavor on a score card provided. The test will result in a maximum (that is, best) total score of 53. The score will be graded by a qualified site staff into a normative percentile score using a provided chart.

Time frame: Up to 12 months

Percentage of Participants With Occurrence of Severe Dysgeusia During the Prophylaxis Treatment Phase

Severe Dysgeusia is defined as a total WETT score of 10th percentile or below according to the normative WETT-SA53 percentile table. Taste assessment will be performed using taste strips (WETT). Four concentrations (4=lowest concentration, 1=highest concentration) will be used for each taste quality: sweet, sour, salty, bitter, and umami. Each test kit contains 53 taste strips distributed in 4 packs; and each taste strip is numbered (1 through 53). Participants will use each strip sequentially and record the flavor on a score card provided. The test will result in a maximum (that is, best) total score of 53. The score will be graded by a qualified site staff into a normative percentile score using a provided chart.

Time frame: Up to 12 months

Time to the First Onset of Severe Dysgeusia During the Prophylaxis Treatment Phase

Time to the first onset of severe dysgeusia is defined as time from the first dose date of talquetamab to the first onset date of severe dysgeusia according to the total WETT score. For participants without severe dysgeusia, time to the first onset will be censored. Taste assessment will be performed using taste strips (WETT). Four concentrations (4=lowest concentration, 1=highest concentration) will be used for each taste quality: sweet, sour, salty, bitter, and umami. Each test kit contains 53 taste strips distributed in 4 packs; and each taste strip is numbered (1 through 53). Participants will use each strip sequentially and record the flavor on a score card provided. The test will result in a maximum (that is, best) total score of 53. The score will be graded by a qualified site staff into a normative percentile score using a provided chart.

Central Contacts

Study Contact

CONTACT

844-434-4210 Participate-In-This-Study1@its.jnj.com

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

University of California San Francisco

San Francisco, California, United States

RECRUITING

Colorado Blood Cancer Institute

Denver, Colorado, United States

RECRUITING

Yale University School Of Medicine

New Haven, Connecticut, United States

RECRUITING

Icahn School of Medicine at Mt. Sinai

New York, New York, United States

RECRUITING

University of Rochester Medical Center

Rochester, New York, United States

RECRUITING

Duke University Medical Center

Durham, North Carolina, United States

RECRUITING

University Hospitals Cleveland Medical Center

Cleveland, Ohio, United States

RECRUITING

Virginia Commonwealth University - Massey Cancer Center

Richmond, Virginia, United States

RECRUITING

University of Washington

Seattle, Washington, United States

RECRUITING

IDOR - Regional Brasilia

Brasília, Brazil

RECRUITING

...and 28 more locations

Secondary Outcomes

Change From Baseline in WETT Testing Score Over Time

Taste assessment will be performed using taste strips (WETT). Four concentrations (4=lowest concentration, 1=highest concentration) will be used for each taste quality: sweet, sour, salty, bitter, and umami. Each test kit contains 53 taste strips distributed in 4 packs; and each taste strip is numbered (1 through 53). Participants will use each strip sequentially and record the flavor on a score card provided. The test will result in a maximum (that is, best) total score of 53.

Time frame: Baseline up to 36 months

Percentage of Time with Dysgeusia During the Prophylaxis Treatment Phase

Time with dysgeusia is defined as the accumulative days a participant had dysgeusia according to the total WETT score divided by the total days of talquetamab exposure. Taste assessment will be performed using taste strips (WETT). Four concentrations (4=lowest concentration, 1=highest concentration) will be used for each taste quality: sweet, sour, salty, bitter, and umami. Each test kit contains 53 taste strips distributed in 4 packs; and each taste strip is numbered (1 through 53). Participants will use each strip sequentially and record the flavor on a score card provided. The test will result in a maximum (that is, best) total score of 53. The score will be graded by a qualified site staff into a normative percentile score using a provided chart.

Time frame: Up to 12 months

Percentage of Participants with Treatment-Emergent Oral Toxicities (Dysgeusia, Oral Mucositis, Dysphagia, and Xerostomia) During the Prophylaxis Treatment Phase

Oral toxicity including dysgeusia, oral mucositis, dysphagia, and xerostomia will be graded (including Grade 0 for dysgeusia) based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), Version 5.0. Severity has 5 grades based on CTCAE criteria: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening consequences; and Grade 5: Death.

Time frame: Up to 12 months

Percentage of Participants with Treatment-Emergent Oral Toxicities (Dysgeusia, Oral Mucositis, Dysphagia, and Xerostomia) During the Study

Oral toxicity including dysgeusia, oral mucositis, dysphagia, and xerostomia will be graded (including Grade 0 for dysgeusia) based on NCI-CTCAE, Version 5.0. Severity has 5 grades based on CTCAE criteria: Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening consequences; and Grade 5: Death.

Time frame: Up to 30 days after the last dose of study treatment (that is, approximately up to 36 months)

Time to the First Onset of Treatment-Emergent Oral Toxicities (Dysgeusia, Oral Mucositis, Dysphagia, and Xerostomia)

Time to the first onset of treatment-emergent dysgeusia, oral mucositis, dysphagia, or xerostomia, will be reported.

Time frame: Up to 36 months

Duration of Treatment-emergent Oral Toxicities (Dysgeusia, Oral Mucositis, Dysphagia, and Xerostomia)

Duration of treatment-emergent oral toxicities including dysgeusia, oral mucositis, dysphagia, and xerostomia will be reported in this outcome measure.

Time frame: Up to 36 months

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 Over Time

The EORTC-QLQ-C30 includes 30 items that make up 5 functional scales (physical, role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (pain, fatigue, and nausea/vomiting), and 5 single symptom items (dyspnea, insomnia, appetite loss, constipation, and diarrhea) and a single impact item (financial difficulties). The recall period is 7 days, and responses are reported using verbal and numeric rating scales. The item and scale scores are transformed to a 0 to 100 scale. A high scale score represents a higher response level. A high score for a functional scale represents a high/healthy level of functioning and a high score for the global health status represents high health related quality of life (HRQoL), but a high score for a symptom scale/item represents a high level of symptomatology/problems.

Time frame: From Baseline, up to 12 months (Cohorts A to E); up to 24 months (for Cohort F)

Change From Baseline in the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Oral Health (EORTC-QLQ-OH15) Domains Scores Over Time

The EORTC module QLQ-OH15 is a 15-item, well-accepted, and validated assessment tool focusing on oral problems and quality of life. The recall period for symptoms is 7 days and response options include 'not at all', "a little', 'quite a bit', and 'very much'. All of the items' measures range in score from 0 to 100. A high score for the symptom items represents a high level of symptomatology or problems.

Time frame: From Baseline, up to 12 months (Cohorts A to E); up to 24 months (for Cohort F)

Percentage of Participants Reporting Oral Symptoms Using the Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)

PRO-CTCAE is a patient-reported item custom survey used to evaluate symptomatic treatment-emergent adverse events in participants on cancer clinical trials. The PRO-CTCAE custom survey consists of 18 items. Responses are provided on a 5-point Likert scale that ranges from 0 to 4. The recall period for symptoms is 7 days. Higher scores indicating greater severity/impact.

Time frame: Up to 12 months (Cohorts A to E); Up to 24 months (for Cohort F)

Percentage of Participants Reporting Oral Symptoms Using the Short Xerostomia Inventory (SXI) Score

SXI is a validated questionnaire that explores how the participant experiences dry mouth (xerostomia) with 5 questions extracted from the original XI. Respondents are asked to choose 1 of 5 responses ("1-Never; 2-Hardly ever; 3-Occasionally; 4-Fairly often; and 5-Very often") to specific statements referring to the preceding 4 weeks. Each individual's responses are scored and summed to give a single XI score. Higher scores represent more severe symptoms.

Time frame: Up to 12 months (Cohorts A to E); Up to 24 months (for Cohort F)

Percentage of Participants Reporting Oral Symptoms Using the Epstein Taste Survey (ETS)

The Epstein Taste Survey (ETS) consists of 17 items PRO instrument, specific to taste and smell changes. The ETS was developed for use in participants with head and neck cancer. This instrument will be used to measure treatment-related symptoms associated with talquetamab.

Time frame: Up to 12 months (Cohorts A to E); Up to 24 months (for Cohort F)

Percentage of Participants Reporting Oral Symptoms Using the Scale of Subjective Total Taste Acuity (STTA)

The STTA is a tool to assess the overall acuity of taste based on a 4-point scale, where 0 reflects no change and 4 represents almost complete loss of taste function. Higher score indicating severity.

Time frame: Up to 12 months (Cohorts A to E); Up to 24 months (for Cohort F)

Change from Baseline in Body Weight Over Time

Change from baseline in body weight will be reported.

Time frame: From Baseline up to 36 months

Change from Baseline in Body Mass Index (BMI) Over Time

Change from baseline in BMI will be reported.

Time frame: From Baseline up to 36 months

Percentage of Participants With Dose Reductions, Interruptions, and Discontinuations For Talquetamab and Ramantamig

Percentage of participants with dose reductions, dose interruptions, and dose discontinuations will be reported.

Time frame: Up to 12 months (Cohorts A to E); Up to 24 months (for Cohort F)

Change from Baseline in Smell Identification Test Score

Smell identification testing will be performed using 4 booklets each containing 10 labels that will release a distinctive scent when scraped with a pencil. Participants will choose the appropriate scent from the associated options. The minimum possible score is a 0 and the maximum is a 40. A higher score indicates better smell/outcome.

Time frame: Baseline (Day 1 Cycle 1), Day 1 Cycle 2 (each cycle duration=28-days)

Percentage of Participants With Overall Response Rate

Overall response rate is defined as the participants with a partial response (PR) or better according to the International Myeloma Working Group (IMWG) criteria.

Time frame: Up to 36 months

Percentage of Participants With Complete Response (CR) or Better Response

CR or better response is defined as the participants who achieve a CR or better response according to the IMWG criteria.

Time frame: Up to 36 months

Percentage of Participants With Very Good Partial Response (VGPR) or Better Response

VGPR or better response is defined as the percentage of participants who achieve a VGPR or better response according to the IMWG criteria.

Time frame: Up to 36 months

Duration of Response (DOR)

Duration of response is defined as time from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the IMWG criteria, or death due to any reason, whichever occurs first.

Time frame: Up to 36 months

Time to Response (TTR)

Time to response is defined as the time between date of first dose of talquetamab or ramantamig and the first efficacy evaluation at which the participant has met all criteria for PR or better.

Time frame: Up to 36 months

Progression-free Survival (PFS)

PFS is defined as the time from the date of first dose of talquetamab or ramantamig to the date of first documented disease progression, as defined in the IMWG criteria, or death due to any cause, whichever occurs first.

Time frame: Up to 36 months

Number of Participants with Treatment-emergent Adverse Event (TEAEs)

An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. Any AE occurring at or after the initial administration of study treatment through the day of last dose plus 30 days, or if beyond 30 days from last dose but is study treatment-related, is considered to be treatment-emergent.

Time frame: Up to 36 months