A Study of Comparing Talquetamab to Belantamab Mafodotin in Participants With Relapsed/Refractory Multiple Myeloma (MonumenTAL-5)

• ClinicalTrials.gov Identifier: NCT05461209
• Recruitment Status: Withdrawn
• First Posted: July 18, 2022
• Last Update Posted: January 30, 2023
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

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).

Condition or disease	Intervention/treatment	Phase
Relapsed/ Refractory Multiple Myeloma	Drug: Talquetamab; Drug: Belantamab Mafodotin	Phase 3

Expanded Access : An investigational treatment associated with this study is no longer available outside the clinical trial.   More info ...

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 0 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: October 20, 2022
• Actual Primary Completion Date: November 15, 2022
• Actual Study Completion Date: November 15, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Arm A: Talquetamab; Participants will receive talquetamab subcutaneously (SC).	Drug: Talquetamab; Talquetamab will be administered as subcutaneous injection.; Other Name: JNJ-64407564
Active Comparator: Arm B: Belantamab Mafodotin; Participants will receive belantamab intravenously (IV).	Drug: Belantamab Mafodotin; Belantamab Mafodotin will be administered as intravenous infusion.

Outcome Measures

Primary Outcome Measures :

1. Overall Response Rate (ORR) [ Time Frame: Up to 1 year 3 months ]
   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.
2. Progression-free Survival (PFS) [ Time Frame: Up to 1 year 3 months ]
   PFS is defined as the duration from the date of randomization to either progressive disease or death, whichever comes first.

Secondary Outcome Measures :

1. Very Good Partial Response (VGPR) or Better Response Rate [ Time Frame: Up to 4 years ]
   VGPR or better response rate is defined as percentage of participants with best overall response of VGPR or better according to IMWG criteria.
2. Complete Response (CR) or Better Response Rate [ Time Frame: Up to 4 years ]
   CR or better response is defined as percentage of participants with best overall response of CR or better according to IMWG criteria.
3. Overall Survival (OS) [ Time Frame: Up to 4 years ]
   OS is defined as the time from randomization to date of death due to any cause.
4. Time to Progression on the First Subsequent Line of Therapy or Death, Whichever Comes First (PFS2) [ Time Frame: Up to 4 years ]
   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.
5. Number of Participants with Adverse Events (AEs) [ Time Frame: Up to 4 years ]
   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.
6. Number of Participants with AEs by Severity [ Time Frame: Up to 4 years ]
   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.
7. Number of Participants with Abnormalities in Clinical Laboratory Assessments [ Time Frame: Up to 4 years ]
   Number of participants with abnormalities in clinical laboratory assessments (such as serum chemistry and hematology [including coagulation]) will be reported.
8. Serum Concentration of Talquetamab [ Time Frame: Up to 4 years ]
   Serum samples will be analyzed to determine concentrations of talquetamab using a validated, specific, and sensitive electrochemiluminescent immunoassay (ECLIA) method.
9. Number of Participants with Anti-drug Antibodies (ADAs) to Talquetamab [ Time Frame: Up to 4 years ]
   Number of participants with ADAs to talquetamab will be reported.
10. Titers of ADAs to Talquetamab [ Time Frame: Up to 4 years ]
    Titers of ADAs to talquetamab will be reported.
11. Change from Baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) [ Time Frame: Baseline up to 4 years ]
    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.
12. Change from Baseline in EuroQol 5-Dimension Questionnaire 5-Level (EQ-5D-5L) [ Time Frame: Baseline up to 4 years ]
    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).
13. Change from Baseline in EuroQol 5-Dimension Questionnaire 5-Level (FACT-G) [ Time Frame: Baseline up to 4 years ]
    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.
14. Time to Sustained Worsening in EORTC-QLQ-C30 [ Time Frame: Up to 4 years ]
    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.
15. Time to Sustained Worsening in EQ-5D-5L [ Time Frame: Up to 4 years ]
    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).
16. Time to Sustained Worsening in FACT-G [ Time Frame: Up to 4 years ]
    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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

United States, Arkansas

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States, 72205

Poland

Swietokrzyskie Centrum Onkologii SPZOZ w Kielcach

Kielce, Poland, 25-734

Sponsors and Collaborators

Janssen Research & Development, LLC

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

More Information

• Responsible Party: Janssen Research & Development, LLC
• ClinicalTrials.gov Identifier: NCT05461209
• Other Study ID Numbers: CR109235; 2022-001442-38 ( EudraCT Number ); 64407564MMY3008 ( Other Identifier: Janssen Research and Development, LLC )
• First Posted: July 18, 2022
• Last Update Posted: January 30, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• 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
• URL: https://www.janssen.com/clinical-trials/transparency

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Multiple Myeloma; Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases