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

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

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).

Study Overview

• Status: Withdrawn
• Conditions: Relapsed/ Refractory Multiple Myeloma
• Intervention / Treatment: Drug: Talquetamab; Drug: Belantamab Mafodotin

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 Type: Interventional
• Phase: Phase 3

Expanded Access

Available outside the clinical trial. See expanded access record.

Contacts and Locations

Study Locations

• Poland
  • Kielce, Poland, 25-734
    • Swietokrzyskie Centrum Onkologii SPZOZ w Kielcach
• United States
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • University of Arkansas for Medical Sciences

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A: Talquetamab; Participants will receive talquetamab subcutaneously (SC).	Drug: Talquetamab; Talquetamab will be administered as subcutaneous injection.; Other Names: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 1 year 3 months
Progression-free Survival (PFS)	PFS is defined as the duration from the date of randomization to either progressive disease or death, whichever comes first.	Up to 1 year 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 4 years
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.	Up to 4 years
Overall Survival (OS)	OS is defined as the time from randomization to date of death due to any cause.	Up to 4 years
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.	Up to 4 years
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.	Up to 4 years
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.	Up to 4 years
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.	Up to 4 years
Serum Concentration of Talquetamab	Serum samples will be analyzed to determine concentrations of talquetamab using a validated, specific, and sensitive electrochemiluminescent immunoassay (ECLIA) method.	Up to 4 years
Number of Participants with Anti-drug Antibodies (ADAs) to Talquetamab	Number of participants with ADAs to talquetamab will be reported.	Up to 4 years
Titers of ADAs to Talquetamab	Titers of ADAs to talquetamab will be reported.	Up to 4 years
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.	Baseline up to 4 years
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).	Baseline up to 4 years
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.	Baseline up to 4 years
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.	Up to 4 years
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).	Up to 4 years
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.	Up to 4 years

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): October 20, 2022
• Primary Completion (Actual): November 15, 2022
• Study Completion (Actual): November 15, 2022

Study Registration Dates

• First Submitted: July 13, 2022
• First Submitted That Met QC Criteria: July 13, 2022
• First Posted (Actual): July 18, 2022

Study Record Updates

• Last Update Posted (Estimate): January 30, 2023
• Last Update Submitted That Met QC Criteria: January 27, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: CR109235; 2022-001442-38 (EudraCT Number); 64407564MMY3008 (Other Identifier: Janssen Research and Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No