Back to resultsA Study of Comparing Talquetamab to Belantamab Mafodotin in Participants With Relapsed/Refractory Multiple Myeloma (MonumenTAL-5)
Primary Purpose
Relapsed/ Refractory Multiple Myeloma
Status
Withdrawn
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Talquetamab
Belantamab Mafodotin
Sponsored by
About this trial
This is an interventional treatment trial for Relapsed/ Refractory Multiple Myeloma
Eligibility Criteria
Inclusion Criteria:
- Documented multiple myeloma as defined by the criteria: a) multiple myeloma according to international myeloma working group (IMWG) diagnostic criteria b) measurable disease at screening, as assessed by central laboratory, defined by any of the following i) serum M-protein level greater than or equal to (>=) 1.0 gram per deciliter (g/dL) ii) urine M-protein level >=200 milligram (mg)/24 hours iii) Light chain multiple myeloma without measurable M-protein in the serum or the urine: serum free light chain (sFLC) >=10 milligram per deciliter (mg/dL) (central laboratory) and abnormal serum immunoglobulin kappa lambda free light chain (FLC) ratio
- Received at least 4 prior antimyeloma therapies including an anti-cluster of differentiation 38 (CD38) monoclonal antibody (mAb) (alone or in combination) and is refractory per IMWG criteria to at least one proteasome inhibitor (PI), and one immunomodulatory drug (IMiD)
- 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 (ECOG) performance status of 0 to 2 at screening
- A female participant of childbearing potential must have a negative serum pregnancy test at screening, and must agree to further serum or urine pregnancy tests during the study and within 6 months after receiving the last dose of study treatment
Exclusion Criteria:
- Contraindications or life-threatening known allergies, hypersensitivity, or intolerance to any study drug or its excipients
- Stroke or seizure within 6 months prior to signing informed consent form (ICF)
- Prior or concurrent exposure to belantamab mafodotin
- Current corneal epithelial disease except mild punctate keratopathy
- Known active central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole brain magnetic resonance imaging (MRI) and lumbar cytology are required
Sites / Locations
- University of Arkansas for Medical Sciences
- Swietokrzyskie Centrum Onkologii SPZOZ w Kielcach
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Arm A: Talquetamab
Arm B: Belantamab Mafodotin
Arm Description
Participants will receive talquetamab subcutaneously (SC).
Participants will receive belantamab intravenously (IV).
Outcomes
Primary Outcome Measures
Overall Response Rate (ORR)
ORR is defined as percentage of participants with confirmed best overall response of partial response (PR) or better according to international myeloma working group (IMWG) criteria.
Progression-free Survival (PFS)
PFS is defined as the duration from the date of randomization to either progressive disease or death, whichever comes first.
Secondary Outcome Measures
Very Good Partial Response (VGPR) or Better Response Rate
VGPR or better response rate is defined as percentage of participants with best overall response of VGPR or better according to IMWG criteria.
Complete Response (CR) or Better Response Rate
CR or better response is defined as percentage of participants with best overall response of CR or better according to IMWG criteria.
Overall Survival (OS)
OS is defined as the time from randomization to date of death due to any cause.
Time to Progression on the First Subsequent Line of Therapy or Death, Whichever Comes First (PFS2)
PFS2 is defined as time from randomization to progression on the first subsequent line of therapy or death due to any cause, whichever comes first.
Number of Participants with Adverse Events (AEs)
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.
Number of Participants with AEs by Severity
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. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death related to adverse event.
Number of Participants with Abnormalities in Clinical Laboratory Assessments
Number of participants with abnormalities in clinical laboratory assessments (such as serum chemistry and hematology [including coagulation]) will be reported.
Serum Concentration of Talquetamab
Serum samples will be analyzed to determine concentrations of talquetamab using a validated, specific, and sensitive electrochemiluminescent immunoassay (ECLIA) method.
Number of Participants with Anti-drug Antibodies (ADAs) to Talquetamab
Number of participants with ADAs to talquetamab will be reported.
Titers of ADAs to Talquetamab
Titers of ADAs to talquetamab will be reported.
Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30)
The EORTC-QLQ-C30 Version 3 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 ("past week"), and responses are reported using a 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.
Change from Baseline in EuroQol 5-Dimension Questionnaire 5-Level (EQ-5D-5L)
EQ-5D-5L is a generic measure of health status. For purposes of this study, the EQ-5D-5L will be used to generate utility scores for use in cost-effectiveness analyses. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).
Change from Baseline in EuroQol 5-Dimension Questionnaire 5-Level (FACT-G)
FACT-G is a 27-item questionnaire designed to measure 4 domains of HRQoL in cancer patients: physical, social, emotional, and functional well-being. In its Physical Well-Being subscale, the FACT-G includes a question concerning side effect bother (item GP5: "I am bothered by side effects of treatment"), rated on a 5-point Likert scale from "not at all" to "very much." This single item will be included as an overall summary measure of the burden of treatment toxicities compared with each other.
Time to Sustained Worsening in EORTC-QLQ-C30
EORTC-QLQ-C30 Version 3 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 ("past week"), and responses are reported using a 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.
Time to Sustained Worsening in EQ-5D-5L
The EuroQol 5-Dimension Questionnaire 5-Level (EQ-5D-5L) is a generic measure of health status. For purposes of this study, the EQ-5D-5L will be used to generate utility scores for use in cost-effectiveness analyses. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).
Time to Sustained Worsening in FACT-G
FACT-G is a 27-item questionnaire designed to measure 4 domains of HRQoL in cancer patients: physical, social, emotional, and functional well-being. In its Physical Well-Being subscale, the FACT-G includes a question concerning side effect bother (item GP5: "I am bothered by side effects of treatment"), rated on a 5-point Likert scale from "not at all" to "very much." This single item will be included as an overall summary measure of the burden of treatment toxicities compared with each other.
Full Information
NCT ID
NCT05461209
First Posted
July 13, 2022
Last Updated
January 27, 2023
Sponsor
Janssen Research & Development, LLC
1. Study Identification
Unique Protocol Identification Number
NCT05461209
Brief Title
A Study of Comparing Talquetamab to Belantamab Mafodotin in Participants With Relapsed/Refractory Multiple Myeloma
Acronym
MonumenTAL-5
Official Title
A Phase 3 Study Comparing Talquetamab to Belantamab Mafodotin in Participants With Relapsed/Refractory Multiple Myeloma Who Have Received at Least 4 Prior Therapies Including an Immunomodulatory Drug, a Proteasome Inhibitor, and an Anti-CD38 Antibody
Study Type
Interventional
2. Study Status
Record Verification Date
January 2023
Overall Recruitment Status
Withdrawn
Why Stopped
Business Decision
Study Start Date
October 20, 2022 (Actual)
Primary Completion Date
November 15, 2022 (Actual)
Study Completion Date
November 15, 2022 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Janssen Research & Development, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to compare the efficacy of talquetamab versus belantamab mafodotin in terms of overall response rate (ORR) or progression-free survival (PFS).
Detailed Description
Multiple myeloma is an incurable, malignant, plasma cell disorder that accounts for approximately 18 percent (%) of hematological malignancies, making it the second most common hematologic malignancy. Talquetamab (also known as JNJ-64407564) is a humanized immunoglobulin G4 (IgG4) bispecific antibody designed to target G Protein-coupled receptor family C group 5 member D (GPRC5D+) cells and cluster of differentiation 3 (CD3) receptor complex on T-cells. Belantamab mafodotin is a humanized B-cell maturation antigen (BCMA)-targeting monoclonal antibody (mAb) conjugated to a cytotoxic agent maleimidocaproyl monomethyl auristatin F (MMAF) which disrupts the microtubule network, leading to cell cycle arrest and apoptosis. This study will investigate the possible improvement of ORR or PFS with talquetamab compared with belantamab mafodotin in participants with relapsed or refractory multiple myeloma who have received at least 4 prior therapies including an anti-CD38 mAb (alone or in combination), and whose disease is refractory to at least one proteasome inhibitor (PI) and one immunomodulatory drug (IMiD). The study will consists of a screening phase, treatment phase (until confirmed progressive disease, start of subsequent antimyeloma therapy, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs first), and post-treatment follow-up phase (until death, withdrawal of consent, loss to follow-up, or end of the study, whichever occurs first). Safety evaluations will include a review of adverse events, physical examinations, eastern cooperative oncology group (ECOG) performance status, clinical laboratory tests, and vital signs.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Relapsed/ Refractory Multiple Myeloma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm A: Talquetamab
Arm Type
Experimental
Arm Description
Participants will receive talquetamab subcutaneously (SC).
Arm Title
Arm B: Belantamab Mafodotin
Arm Type
Active Comparator
Arm Description
Participants will receive belantamab intravenously (IV).
Intervention Type
Drug
Intervention Name(s)
Talquetamab
Other Intervention Name(s)
JNJ-64407564
Intervention Description
Talquetamab will be administered as subcutaneous injection.
Intervention Type
Drug
Intervention Name(s)
Belantamab Mafodotin
Intervention Description
Belantamab Mafodotin will be administered as intravenous infusion.
Primary Outcome Measure Information:
Title
Overall Response Rate (ORR)
Description
ORR is defined as percentage of participants with confirmed best overall response of partial response (PR) or better according to international myeloma working group (IMWG) criteria.
Time Frame
Up to 1 year 3 months
Title
Progression-free Survival (PFS)
Description
PFS is defined as the duration from the date of randomization to either progressive disease or death, whichever comes first.
Time Frame
Up to 1 year 3 months
Secondary Outcome Measure Information:
Title
Very Good Partial Response (VGPR) or Better Response Rate
Description
VGPR or better response rate is defined as percentage of participants with best overall response of VGPR or better according to IMWG criteria.
Time Frame
Up to 4 years
Title
Complete Response (CR) or Better Response Rate
Description
CR or better response is defined as percentage of participants with best overall response of CR or better according to IMWG criteria.
Time Frame
Up to 4 years
Title
Overall Survival (OS)
Description
OS is defined as the time from randomization to date of death due to any cause.
Time Frame
Up to 4 years
Title
Time to Progression on the First Subsequent Line of Therapy or Death, Whichever Comes First (PFS2)
Description
PFS2 is defined as time from randomization to progression on the first subsequent line of therapy or death due to any cause, whichever comes first.
Time Frame
Up to 4 years
Title
Number of Participants with Adverse Events (AEs)
Description
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.
Time Frame
Up to 4 years
Title
Number of Participants with AEs by Severity
Description
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. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death related to adverse event.
Time Frame
Up to 4 years
Title
Number of Participants with Abnormalities in Clinical Laboratory Assessments
Description
Number of participants with abnormalities in clinical laboratory assessments (such as serum chemistry and hematology [including coagulation]) will be reported.
Time Frame
Up to 4 years
Title
Serum Concentration of Talquetamab
Description
Serum samples will be analyzed to determine concentrations of talquetamab using a validated, specific, and sensitive electrochemiluminescent immunoassay (ECLIA) method.
Time Frame
Up to 4 years
Title
Number of Participants with Anti-drug Antibodies (ADAs) to Talquetamab
Description
Number of participants with ADAs to talquetamab will be reported.
Time Frame
Up to 4 years
Title
Titers of ADAs to Talquetamab
Description
Titers of ADAs to talquetamab will be reported.
Time Frame
Up to 4 years
Title
Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30)
Description
The EORTC-QLQ-C30 Version 3 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 ("past week"), and responses are reported using a 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.
Time Frame
Baseline up to 4 years
Title
Change from Baseline in EuroQol 5-Dimension Questionnaire 5-Level (EQ-5D-5L)
Description
EQ-5D-5L is a generic measure of health status. For purposes of this study, the EQ-5D-5L will be used to generate utility scores for use in cost-effectiveness analyses. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).
Time Frame
Baseline up to 4 years
Title
Change from Baseline in EuroQol 5-Dimension Questionnaire 5-Level (FACT-G)
Description
FACT-G is a 27-item questionnaire designed to measure 4 domains of HRQoL in cancer patients: physical, social, emotional, and functional well-being. In its Physical Well-Being subscale, the FACT-G includes a question concerning side effect bother (item GP5: "I am bothered by side effects of treatment"), rated on a 5-point Likert scale from "not at all" to "very much." This single item will be included as an overall summary measure of the burden of treatment toxicities compared with each other.
Time Frame
Baseline up to 4 years
Title
Time to Sustained Worsening in EORTC-QLQ-C30
Description
EORTC-QLQ-C30 Version 3 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 ("past week"), and responses are reported using a 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.
Time Frame
Up to 4 years
Title
Time to Sustained Worsening in EQ-5D-5L
Description
The EuroQol 5-Dimension Questionnaire 5-Level (EQ-5D-5L) is a generic measure of health status. For purposes of this study, the EQ-5D-5L will be used to generate utility scores for use in cost-effectiveness analyses. The EQ-5D-5L is a 5-item questionnaire that assesses 5 domains including mobility, self-care, usual activities, pain/discomfort and anxiety/depression plus a visual analog scale rating "health today" with anchors ranging from 0 (worst imaginable health state) to 100 (best imaginable health state).
Time Frame
Up to 4 years
Title
Time to Sustained Worsening in FACT-G
Description
FACT-G is a 27-item questionnaire designed to measure 4 domains of HRQoL in cancer patients: physical, social, emotional, and functional well-being. In its Physical Well-Being subscale, the FACT-G includes a question concerning side effect bother (item GP5: "I am bothered by side effects of treatment"), rated on a 5-point Likert scale from "not at all" to "very much." This single item will be included as an overall summary measure of the burden of treatment toxicities compared with each other.
Time Frame
Up to 4 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Documented multiple myeloma as defined by the criteria: a) multiple myeloma according to international myeloma working group (IMWG) diagnostic criteria b) measurable disease at screening, as assessed by central laboratory, defined by any of the following i) serum M-protein level greater than or equal to (>=) 1.0 gram per deciliter (g/dL) ii) urine M-protein level >=200 milligram (mg)/24 hours iii) Light chain multiple myeloma without measurable M-protein in the serum or the urine: serum free light chain (sFLC) >=10 milligram per deciliter (mg/dL) (central laboratory) and abnormal serum immunoglobulin kappa lambda free light chain (FLC) ratio
Received at least 4 prior antimyeloma therapies including an anti-cluster of differentiation 38 (CD38) monoclonal antibody (mAb) (alone or in combination) and is refractory per IMWG criteria to at least one proteasome inhibitor (PI), and one immunomodulatory drug (IMiD)
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 (ECOG) performance status of 0 to 2 at screening
A female participant of childbearing potential must have a negative serum pregnancy test at screening, and must agree to further serum or urine pregnancy tests during the study and within 6 months after receiving the last dose of study treatment
Exclusion Criteria:
Contraindications or life-threatening known allergies, hypersensitivity, or intolerance to any study drug or its excipients
Stroke or seizure within 6 months prior to signing informed consent form (ICF)
Prior or concurrent exposure to belantamab mafodotin
Current corneal epithelial disease except mild punctate keratopathy
Known active central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, negative whole brain magnetic resonance imaging (MRI) and lumbar cytology are required
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janssen Research & Development, LLC Clinical Trial
Organizational Affiliation
Janssen Research & Development, LLC
Official's Role
Study Director
Facility Information:
Facility Name
University of Arkansas for Medical Sciences
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
Swietokrzyskie Centrum Onkologii SPZOZ w Kielcach
City
Kielce
ZIP/Postal Code
25-734
Country
Poland
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
IPD Sharing URL
https://www.janssen.com/clinical-trials/transparency
Learn more about this trial
A Study of Comparing Talquetamab to Belantamab Mafodotin in Participants With Relapsed/Refractory Multiple Myeloma
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