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

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Not yet recruiting
CT.gov ID
NCT05461209
Collaborator
(none)
216
Enrollment
76
Locations
2
Arms
47
Anticipated Duration (Months)
2.8
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

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
Phase 3

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
Anticipated Enrollment :
216 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
Anticipated Study Start Date :
Nov 8, 2022
Anticipated Primary Completion Date :
Feb 22, 2024
Anticipated Study Completion Date :
Oct 9, 2026

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 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.

    Outcome Measures

    Primary Outcome Measures

    1. Overall Response Rate (ORR) [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) [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 [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 [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) [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) [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) [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 [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 [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 [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 [Up to 4 years]

      Number of participants with ADAs to talquetamab will be reported.

    10. Titers of ADAs to Talquetamab [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) [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) [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) [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 [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 [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 [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

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Site City State Country Postal Code
    1 Highlands Oncology Group Fayetteville Arkansas United States 72703
    2 The University of Arkansas for Medical Sciences Myeloma Institute for Research and Therapy Little Rock Arkansas United States 72205
    3 University of California, San Francisco San Francisco California United States 94143
    4 MedStar Georgetown University Hospital Washington District of Columbia United States 20007
    5 Walter Reed National Military Medical Center Bethesda Maryland United States 20814
    6 Beth Israel Deaconess Medical Center Boston Massachusetts United States 02215
    7 Karmanos Cancer Institute Detroit Michigan United States 48201-2013
    8 Mayo Clinic Rochester Rochester Minnesota United States 55905
    9 New Jersey Hematology Oncology Ass. Brick New Jersey United States 08724
    10 Novant Health Charlotte North Carolina United States 28204
    11 Novant Health Winston-Salem North Carolina United States 27103
    12 University Hospital of Cleveland Cleveland Ohio United States 44106
    13 University of Pennsylvania Philadelphia Pennsylvania United States 19104
    14 University of Texas Southwestern Medical Center Dallas Texas United States 75390
    15 Huntsman Cancer Institute Salt Lake City Utah United States 84112
    16 University of Wisconsin Carbone Cancer Center Madison Wisconsin United States 53705
    17 Medical College Of Wisconsin Milwaukee Wisconsin United States 53226-3522
    18 Nova Scotia Health Authority Halifax Nova Scotia Canada B3H 1V7
    19 University Health Network Toronto Ontario Canada M5G 1Z5
    20 CIUSSS de l'Est-de-l'Île-de-Montréal Installation Hôpital Maisonneuve-Rosemont Montreal Quebec Canada H1T 2M4
    21 CHU de Québec Université Laval Quebec Canada G1R 2J6
    22 Fakultni nemocnice Brno Brno Czechia 625 00
    23 Fakultni nemocnice Hradec Kralove Hradec Kralove Czechia 500 05
    24 Fakultní nemocnice Olomouc Olomouc Czechia 779 00
    25 Fakultni nemocnice Ostrava Ostrava Czechia 708 52
    26 Universitaetsklinikum Frankfurt Frankfurt Germany 60590
    27 Universitaetsklinikum Halle (Saale) Halle (Saale) Germany 06120
    28 Universitaetsklinikum Schleswig-Holstein Campus Kiel Kiel Germany 24105
    29 Universitaetsklinikum Koeln Koeln Germany 50937
    30 Klinikum rechts der Isar der TU Muenchen Muenchen Germany 81675
    31 Universitaetsklinikum Tuebingen der Eberhard-Karls-Universitaet, Abteilung fuer Innere Medizin II, Tuebingen Germany 72076
    32 Universitaetsklinikum Wuerzburg Wuerzburg Germany 97080
    33 Rambam Medical Center Haifa Israel 3109601
    34 Carmel Medical Center Haifa Israel 3436212
    35 Rabin Medical Center Petah Tikva Israel 49100
    36 Sheba Medical Center Ramat Gan Israel 52621
    37 Policlinico Sant'Orsola Malpighi Bologna Italy 40138
    38 Asst Ovest Milanese - Ospedale Di Legnano Legnano Italy 20025
    39 Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori Meldola Italy 47014
    40 Fondazione IRCCS Cà Granda, Ospedale Policlinico di Milano Milano Italy 20122
    41 Fondazione IRCCS Istituto Nazionale dei Tumori Milano Italy 20133
    42 Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone Palermo Italy 90127
    43 Fondazione IRCCS Policlinico San Matteo Pavia Italy 27100
    44 Azienda Ospedaliera di Perugia Ospedale S.Maria della Misericordia Perugia Italy 06129
    45 A.O. Universitaria Senese- Ospedale Santa Maria alle Scotte Siena Italy 53100
    46 Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino Torino Italy 10126
    47 Ospedale S.Maria della Misericordia, Oncologia Medica Udine Italy 33100
    48 Ospedale di Circolo - Fondazione Macchi Varese Italy 21100
    49 Szpital Specjalistyczny w Brzozowie Podkarpacki Osrodek Onkologiczny im. Ks. B. Markiewicza Brzozów Poland 36-200
    50 Swietokrzyskie Centrum Onkologii SPZOZ w Kielcach Kielce Poland 25-734
    51 Szpital Kliniczny im. H. Swiecickiego Uniwersytetu Medycznego im. K. Marcinkowskiego w Poznaniu Poznań Poland 60-101
    52 Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy Warszawa Poland 02-781
    53 Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu Wroclaw Poland 50-367
    54 Hosp. Garcia de Orta Almada Portugal 2805-267
    55 Instituto Portugues de Oncologia Lisboa Portugal 1099-023
    56 Champalimaud Foundation Champalimaud Centre Lisbon Portugal 1400-038
    57 Instituto Portugues de Oncologia Porto Portugal 4200-072
    58 Centro Hospitalar Vila Nova de Gaia Vila Nova de Gaia Portugal 4434-502
    59 Hosp. de Cabuenes Asturias Spain
    60 Hosp. Univ. Germans Trias I Pujol Badalona Spain 08916
    61 Hosp. Univ. Vall D Hebron Barcelona Spain 08035
    62 Hosp. Clinic I Provincial de Barcelona Barcelona Spain 08036
    63 Hosp. de Leon Leon Spain 24071
    64 Hosp. Univ. de La Princesa Madrid Spain 28006
    65 Hosp. Gral. Univ. Gregorio Marañon Madrid Spain 28007
    66 Hosp. Quiron Madrid Pozuelo Madrid Spain 28223
    67 Hosp. Univ. Virgen de La Arrixaca Murcia Spain 30120
    68 Hosp. Univ. Marques de Valdecilla Santander Spain 39008
    69 Hosp. Gral. Univ. de Toledo Toledo Spain 45007
    70 Hosp. Univ. Dr. Peset Valencia Spain 46017
    71 Belfast City Hospital Belfast United Kingdom BT9 7AB
    72 Nottingham University Hospitals Nottingham United Kingdom NG5 1PB
    73 Derriford Hospital Plymouth United Kingdom PL6 8DH
    74 Queen Alexandra Hospital Porthsmouth United Kingdom PO6 3LY
    75 Royal Marsden Hospital Sutton United Kingdom SM2 5PT
    76 New Cross Hospital Wolverhampton United Kingdom WV10 0QP

    Sponsors and Collaborators

    • Janssen Research & Development, LLC

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Janssen Research & Development, LLC
    ClinicalTrials.gov Identifier:
    NCT05461209
    Other Study ID Numbers:
    • CR109235
    • 2022-001442-38
    • 64407564MMY3008
    First Posted:
    Jul 18, 2022
    Last Update Posted:
    Aug 12, 2022
    Last Verified:
    Aug 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    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

    Study Results

    No Results Posted as of Aug 12, 2022