A Phase 2, Open-label, Randomized Study to Evaluate GPRC5D-related Oral Events
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 210
- 试验地点
- 65
- 主要终点
- Percentage of Participants With Occurrence of Dysgeusia as Assessed by the Total Waterless Empirical Taste Test (WETT) Testing Score During the Prophylaxis Treatment Phase
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Cohort B: Prophylaxis A and Talquetamab
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.
干预措施: Prophylaxis A (Drug)
Cohort C: Prophylaxis B and Talquetamab
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.
干预措施: Prophylaxis B (Drug)
Cohort E: Prophylaxis D and Talquetamab
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 D along with talquetamab therapy. Participants will start the assigned prophylaxis 1 day 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.
干预措施: Talquetamab (Drug)
Cohort B: Prophylaxis A and Talquetamab
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.
干预措施: Talquetamab (Drug)
Cohort C: Prophylaxis B and Talquetamab
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.
干预措施: Talquetamab (Drug)
Cohort D: Prophylaxis C and Talquetamab
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.
干预措施: Talquetamab (Drug)
Cohort F: Ramantamig
Participants with RRMM who are triple-class exposed (previously exposed to at least 1 PI, 1 IMiD, and an anti-CD38 mAb) will receive single step-up dose of ramantamig subcutaneously followed by the treatment dose until disease progression, death, unacceptable toxicity, withdrawal of consent, discontinuation of ramantamig, or end of study, whichever occurs first.
干预措施: Ramantamig (Drug)
Cohort E: Prophylaxis D and Talquetamab
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 D along with talquetamab therapy. Participants will start the assigned prophylaxis 1 day 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.
干预措施: Prophylaxis D (Drug)
Cohort A: Talquetamab
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.
干预措施: Talquetamab (Drug)
Cohort D: Prophylaxis C and Talquetamab
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.
干预措施: Prophylaxis C (Drug)
结局指标
主要结局
Percentage of Participants With Occurrence of Dysgeusia as Assessed by the Total Waterless Empirical Taste Test (WETT) Testing Score During the Prophylaxis Treatment Phase
时间窗: Up to 12 months
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.
Percentage of Participants With Occurrence of Severe Dysgeusia During the Prophylaxis Treatment Phase
时间窗: Up to 12 months
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.
Percentage of Participants Who Report Resolution/Improvement of Dysgeusia During the Prophylaxis Treatment Phase
时间窗: At Month 6
Resolution/improvement is defined as 2 potential scenarios: 1) A dysgeusia downgraded to dysgeusia-free, that is (i.e.,) total WETT score of 25th percentile or below at visits prior to the end of month 6 becomes total WETT score above 25th percentile at the end of month 6. 2) Severe dysgeusia downgraded to non-severe dysgeusia, i.e., total WETT score of 10th percentile or below prior to the end of month 6 becomes total WETT score above 10th percentile at the end of month 6. Taste assessment will be performed using taste strips (WETT). Four concentrations will be used for each taste quality: sweet, sour, salty, bitter, \& umami. Each test kit contains 53 taste strips; numbered (1 through 53). Participants will use each strip sequentially and record flavor on score card provided. Test will result in maximum (i.e., best) total score of 53. Score will be graded by qualified staff into normative percentile score using provided chart.
Time to the First Onset of Severe Dysgeusia During the Prophylaxis Treatment Phase
时间窗: Up to 12 months
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.
Percentage of Participants Who Report Resolution/Improvement of Dysgeusia During the Prophylaxis Treatment Phase
时间窗: End of Month 3
Resolution/improvement is defined as 2 potential scenarios: 1) A dysgeusia downgraded to dysgeusia-free, that is (i.e.,) total WETT score of 25th percentile or below at visits prior to the end of month 3 becomes total WETT score above 25th percentile at the end of month 3. 2) Severe dysgeusia downgraded to non-severe dysgeusia, i.e., total WETT score of 10th percentile or below prior to the end of month 3 becomes total WETT score above 10th percentile at the end of month 3. Taste assessment will be performed using taste strips (WETT). Four concentrations will be used for each taste quality: sweet, sour, salty, bitter, \& umami. Each test kit contains 53 taste strips; numbered (1 through 53). Participants will use each strip sequentially and record flavor on score card provided. Test will result in maximum (i.e., best) total score of 53. Score will be graded by qualified staff into normative percentile score using provided chart.
Percentage of Participants Who Report Resolution/Improvement of Dysgeusia During the Prophylaxis Treatment Phase
时间窗: End of Month 7
Resolution/improvement is defined as 2 potential scenarios: 1) A dysgeusia downgraded to dysgeusia-free, that is (i.e.,) total WETT score of 25th percentile or below at visits prior to the end of month 7 becomes total WETT score above 25th percentile at the end of month 7. 2) Severe dysgeusia downgraded to non-severe dysgeusia, i.e., total WETT score of 10th percentile or below prior to the end of month 7 becomes total WETT score above 10th percentile at the end of month 7. Taste assessment will be performed using taste strips (WETT). Four concentrations will be used for each taste quality: sweet, sour, salty, bitter, \& umami. Each test kit contains 53 taste strips; numbered (1 through 53). Participants will use each strip sequentially and record flavor on score card provided. Test will result in maximum (i.e., best) total score of 53. Score will be graded by qualified staff into normative percentile score using provided chart.
Percentage of Participants Who Report Resolution/Improvement of Dysgeusia During the Prophylaxis Treatment Phase
时间窗: At Month 3
Resolution/improvement is defined as 2 potential scenarios: 1) A dysgeusia downgraded to dysgeusia-free, that is (i.e.,) total WETT score of 25th percentile or below at visits prior to the end of month 3 becomes total WETT score above 25th percentile at the end of month 3. 2) Severe dysgeusia downgraded to non-severe dysgeusia, i.e., total WETT score of 10th percentile or below prior to the end of month 3 becomes total WETT score above 10th percentile at the end of month 3. Taste assessment will be performed using taste strips (WETT). Four concentrations will be used for each taste quality: sweet, sour, salty, bitter, \& umami. Each test kit contains 53 taste strips; numbered (1 through 53). Participants will use each strip sequentially and record flavor on score card provided. Test will result in maximum (i.e., best) total score of 53. Score will be graded by qualified staff into normative percentile score using provided chart.
次要结局
- Change From Baseline in WETT Testing Score Over Time(Baseline up to 30 months)
- Percentage of Time with Dysgeusia During the Prophylaxis Treatment Phase(Up to 12 months)
- Number of Participants with Treatment-emergent Oral Toxicities (Dysgeusia, Oral Mucositis, Dysphagia, and Xerostomia) During the Prophylaxis Treatment Phase(Up to 12 months)
- Number of Participants with Treatment-emergent Oral Toxicities (Dysgeusia, Oral Mucositis, Dysphagia, and Xerostomia) Over Time(Up to 30 months)
- Time to the First Onset of Treatment-emergent Oral Toxicities (Dysgeusia, Oral Mucositis, Dysphagia, and Xerostomia)(Up to 30 months)
- Duration of Treatment-emergent Oral Toxicities (Dysgeusia, Oral Mucositis, Dysphagia, and Xerostomia)(Up to 30 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(From Baseline up to 30 months)
- 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(From Baseline up to 30 months)
- Percentage of Participants Reporting Oral Symptoms Using the Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)(Up to 12 months)
- Percentage of Participants Reporting Oral Symptoms Using the Short Xerostomia Inventory (SXI) Score(Up to 30 months)
- Percentage of Participants Reporting Oral Symptoms Using the Epstein Taste Survey (ETS)(Up to 30 months)
- Percentage of Participants Reporting Oral Symptoms Using the Scale of Subjective Total Taste Acuity (STTA)(Up to 12 months)
- Change from Baseline in Body Weight Over Time(From Baseline up to 30 months)
- Change from Baseline in Body Mass Index (BMI) Over Time(From Baseline up to 30 months)
- Percentage of Participants With Dose Reductions, Interruptions, and Discontinuations(Up to 12 months)
- Change from Baseline in Smell Identification Test Score(Baseline (Day 1 Cycle 1), Day 1 Cycle 2 (each cycle duration=28-days))
- Change from Baseline in Smell Detection Threshold Test Score(Baseline (Day 1 Cycle 1), Day 1 Cycle 2 (each cycle duration=28-days))
- Percentage of Participants With Overall Response Rate(Up to 30 months)
- Percentage of Participants With Complete Response (CR) or Better Response(Up to 30 months)
- Percentage of Participants With Very Good Partial Response (VGPR) or Better Response(Up to 30 months)
- Duration of Response (DOR)(Up to 30 months)
- Time to Response (TTR)(Up to 30 months)
- Progression-free Survival (PFS)(Up to 30 months)
- Number of Participants with Treatment-emergent Adverse Event (TEAEs)(Up to 30 months)
- Change From Baseline in WETT Testing Score Over Time(Baseline up to 36 months)
- Percentage of Participants with Treatment-Emergent Oral Toxicities (Dysgeusia, Oral Mucositis, Dysphagia, and Xerostomia) During the Prophylaxis Treatment Phase(Up to 12 months)
- Change from Baseline in Body Weight Over Time(From Baseline up to 36 months)
- Percentage of Participants with Treatment-Emergent Oral Toxicities (Dysgeusia, Oral Mucositis, Dysphagia, and Xerostomia) During the Study(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)(Up to 36 months)
- Duration of Treatment-emergent Oral Toxicities (Dysgeusia, Oral Mucositis, Dysphagia, and Xerostomia)(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(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 Scale of Subjective Total Taste Acuity (STTA)(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(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)(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(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)(Up to 12 months (Cohorts A to E); Up to 24 months (for Cohort F))
- Change from Baseline in Body Mass Index (BMI) Over Time(From Baseline up to 36 months)
- Percentage of Participants With Dose Reductions, Interruptions, and Discontinuations For Talquetamab and Ramantamig(Up to 12 months (Cohorts A to E); Up to 24 months (for Cohort F))
- Percentage of Participants With Overall Response Rate(Up to 36 months)
- Percentage of Participants With Complete Response (CR) or Better Response(Up to 36 months)
- Percentage of Participants With Very Good Partial Response (VGPR) or Better Response(Up to 36 months)
- Duration of Response (DOR)(Up to 36 months)
- Time to Response (TTR)(Up to 36 months)
- Progression-free Survival (PFS)(Up to 36 months)
- Number of Participants with Treatment-emergent Adverse Event (TEAEs)(Up to 36 months)