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.

A Study to Evaluate Preventive Treatments for Talquetamab-related Oral Toxicity

Relapse Multiple Myeloma

Relapsed or Refractory Multiple Myeloma

Relapsed/ Refractory Multiple Myeloma

Relapsed/Refractory Multiple Myeloma

Refractory Multiple Myeloma

Relapsed/Refractory Multiple Myeloma (RRMM)

Multiple Myeloma

Kahler's Disease

Blood Cancer

Hematologic Neoplasms

Hematologic Malignancies

Hematology

Hematological Malignancies

Talquetamab

Prophylaxis A

Prophylaxis B

Prophylaxis C

A Phase 2, Open-label, Randomized Study to Evaluate Prophylactic Interventions on Talquetamab-related Oral Toxicity

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.

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 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. 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.

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.

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.

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 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.

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.

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

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

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.

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.

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.

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.

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.

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.

Change from baseline in body weight will be reported.

Change from baseline in BMI will be reported.

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

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.

Smell threshold detection testing will be performed using vials of rose oil (phenyl
ethanol) in vol/vol concentrations ranging from 10^-2 (strongest) through 10^-9
(weakest). Participants will be exposed, one at a time, to pairs of vials and asked to
distinguish which is stronger.

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

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

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

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 disease progression, whichever occurs
first.

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

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

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.

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.

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.

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.

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.

A Study to Evaluate Preventive Treatments for Talquetamab-related Oral Toxicity

Trials at a glance

Trials at a glance

Eligibility criteria