A Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma (MonumenTAL-1)

A Phase 1/2, First-in-Human, Open-Label, Dose Escalation Study of Talquetamab, a Humanized GPRC5D x CD3 Bispecific Antibody, in Subjects With Relapsed or Refractory Multiple Myeloma

The purpose of this study is to evaluate the efficacy and safety of talquetamab in participants with relapsed or refractory multiple myeloma at the recommended Phase 2 dose(s) (RP2Ds) (Part 3).

Study Overview

• Status: Recruiting
• Conditions: Hematological Malignancies
• Intervention / Treatment: Drug: Talquetamab

Detailed Description

Multiple myeloma is a malignant plasma cell disorder characterized by osteolytic lesions, increased susceptibility to infections, hypercalcemia, and renal failure. Talquetamab is a humanized immunoglobulin G4 proline, alanine, alanine (IgG4PAA) bispecific antibody designed to target G protein-coupled receptor family C group 5-member D (GPRC5D) and the CD3 molecule found on T lymphocytes (T cell). This study consists of 3 periods: screening phase (up to 28 days), treatment phase (start of study drug administration and continues until the completion of the end of treatment [EOT (30 days (+ 7 days)] visit); and a post-treatment follow-up phase (until the end of study unless the participant has died, is lost to follow up or has withdrawn consent). Total duration of study is up to 2 years (after the last participant receives their first dose). Safety, pharmacokinetics (PK), laboratory tests, and questionnaire will be assessed at specified time points during this study. Participants safety and study conduct will be monitored throughout the study. The corresponding study (NCT03399799) is the Phase 1 part of the study and TALMMY1001- Part 3 is the Phase 2 part of the study.

• Study Type: Interventional
• Enrollment (Estimated): 450
• Phase: Phase 2

Expanded Access

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Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study@its.jnj.com

Study Locations

• Belgium
  • Brussels, Belgium, 1200
    • Recruiting
    • UCL - Saint Luc
  • Edegem, Belgium, 2650
    • Recruiting
    • UZ Antwerpen
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ Leuven
  • Liège, Belgium, 4000
    • Recruiting
    • CHU de Liège - Domaine Universitaire du Sart Tilman
• China
  • Beijing, China, 100191
    • Recruiting
    • Peking University Third Hospital
  • Guangzhou, China, 510060
    • Recruiting
    • Sun Yat-sen University Cancer Center
  • Hangzhou, China, 310003
    • Active, not recruiting
    • The 1St Affiliated Hospital of Medical College Zhejiang University
  • Hangzhou, China, 310003
    • Recruiting
    • The 1St Affiliated Hospital of Medical College Zhejiang University
  • Su Zhou, China, 215006
    • Recruiting
    • First Affiliated Hospital, SooChow University
  • Tianjin, China, 300320
    • Recruiting
    • Institute of Hematology & Blood Disease Hospital Chinese Academy of Medical Science
  • XI An Shi, China, 710063
    • Recruiting
    • The First Affiliated Hospital of Xian Jiaotong University
  • Xi'an, China, 710004
    • Completed
    • The Second Affiliated Hospital of Xi'an Jiaotong University
• France
  • Creteil, France, 94000
    • Recruiting
    • CHU Henri Mondor
  • Montpellier, France, 34295
    • Recruiting
    • CHU de Montpellier, Hopital Saint-Eloi
  • Nantes, France, 44093
    • Recruiting
    • C.H.U. Hotel Dieu - France
  • Pessac cedex, France, 33604
    • Recruiting
    • CHU de Bordeaux - Hospital Haut-Leveque
  • Pierre Benite cedex, France, 69495
    • Recruiting
    • Centre Hospitalier Lyon-Sud
  • Toulouse cedex 9, France, 31059
    • Recruiting
    • Pôle IUC Oncopole CHU
• Germany
  • Berlin, Germany, 12203
    • Recruiting
    • Charite Campus Benjamin Franklin
  • Heidelberg, Germany, 69120
    • Recruiting
    • Universitaetsklinikum Heidelberg
  • Muenster, Germany, 48149
    • Completed
    • Universitaetsklinikum Muenster
  • Wuerzburg, Germany, 97080
    • Recruiting
    • Universitätsklinikum Würzburg
• Israel
  • Haifa, Israel, 3436212
    • Recruiting
    • Carmel Medical Center
  • Haifa, Israel, 31096
    • Recruiting
    • Rambam Medical Center
  • Jerusalem, Israel, 91120
    • Recruiting
    • Hadassah Medical Center
  • Ramat Gan, Israel, 52621
    • Recruiting
    • Sheba Medical Center
  • Tel Aviv, Israel, 64239
    • Recruiting
    • Tel Aviv Sourasky Medical Center
• Japan
  • Chiba, Japan, 296-8602
    • Recruiting
    • Kameda General Hospital
  • Fukuoka, Japan, 814-0180
    • Active, not recruiting
    • Fukuoka University Hospital
  • Gifu, Japan, 503-8502
    • Active, not recruiting
    • Ogaki Municipal Hospital
  • Hokkaido, Japan, 006-8555
    • Active, not recruiting
    • Teine Keijinkai Hospital
  • Hyogo, Japan, 650-0047
    • Active, not recruiting
    • Kobe City Medical Center General Hospital
  • Koshigaya, Japan, 343-8555
    • Recruiting
    • Dokkyo Medical University Saitama Medical Center
  • Kumamoto, Japan, 860-8556
    • Active, not recruiting
    • Kumamoto University Hospital
  • Kurashiki, Japan, 710-8602
    • Active, not recruiting
    • Kurashiki Central Hospital
  • Matsumoto, Japan, 399-8701
    • Active, not recruiting
    • National Hospital Organization Matsumoto Medical Center
  • Okayama, Japan, 701-1192
    • Active, not recruiting
    • National Hospital Organization Okayama Medical Center
  • Osaka, Japan, 543-8555
    • Active, not recruiting
    • Japanese Red Cross Osaka Hospital
  • Otake, Japan, 739-0696
    • Recruiting
    • Hiroshima West Medical Center
  • Shiwa-gun, Japan, 028-3695
    • Active, not recruiting
    • Iwate Medical University Hospital
• Korea, Republic of
  • Jeollanam-do, Korea, Republic of, 58128
    • Recruiting
    • Chonnam National University Hwasun Hospital
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 06591
    • Recruiting
    • The Catholic University of Korea Seoul St. Mary'S Hospital
  • Seoul, Korea, Republic of, 03722
    • Completed
    • Severance Hospital, Yonsei University Health System
  • Seoul, Korea, Republic of, 05505
    • Completed
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Completed
    • Samsung Medical Center
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Recruiting
    • VU Medisch Centrum
  • Utrecht, Netherlands, 3584 CX
    • Completed
    • UMCU
• Poland
  • Gdansk, Poland, 80-214
    • Active, not recruiting
    • Uniwersyteckie Centrum Kliniczne
  • Gliwice, Poland, 44102
    • Completed
    • Narodowy Instytut Onkologii im.Marii Sklodowskiej Curie Panstwowy Instytut BadawczyOddz. w Gliwicach
  • Poznan, Poland, 60-569
    • Active, not recruiting
    • Uniwersytecki Szpital Kliniczny w Poznaniu
  • Warszawa, Poland, 02-781
    • Active, not recruiting
    • Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy
  • Wroclaw, Poland, 52-007
    • Active, not recruiting
    • Uniwersytecki Szpital Kliniczny Im. Jana Mikulicza-Radeckiego We Wroclawiu
• Spain
  • Badalona, Spain, 08916
    • Recruiting
    • Hosp. Univ. Germans Trias I Pujol
  • Barcelona, Spain, 08035
    • Recruiting
    • Hosp. Univ. Vall D Hebron
  • Barcelona, Spain, 8908
    • Recruiting
    • Inst. Cat. Doncologia-H Duran I Reynals
  • Madrid, Spain, 28041
    • Recruiting
    • Hosp. Univ. 12 de Octubre
  • Madrid, Spain, 28040
    • Completed
    • Hosp. Univ. Fund. Jimenez Diaz
  • Murcia, Spain, 30120
    • Recruiting
    • Hosp. Univ. Virgen de La Arrixaca
  • Pamplona, Spain, 31008
    • Recruiting
    • Clinica Univ. de Navarra
  • Pozuelo de Alarcon, Spain, 28223
    • Recruiting
    • Hosp. Quiron Madrid Pozuelo
  • Salamanca, Spain, 37007
    • Recruiting
    • Hosp. Clinico Univ. de Salamanca
  • Santander, Spain, 39008
    • Recruiting
    • Hosp. Univ. Marques de Valdecilla
  • Sevilla, Spain, 41013
    • Recruiting
    • Hosp. Virgen Del Rocio
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Recruiting
      • University of Alabama Birmingham
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Recruiting
      • University of Arkansas for Medical Sciences
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University - Winship Cancer Institute
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University Of Chicago
  • Kentucky
    • Louisville, Kentucky, United States, 40207
      • Recruiting
      • Norton Cancer Institute
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan Health System
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine
  • New York
    • New York, New York, United States, 10016
      • Recruiting
      • NYU Langone Health
    • New York, New York, United States, 10023
      • Recruiting
      • Mount Sinai Medical Center
    • Rochester, New York, United States, 14642
      • Recruiting
      • University of Rochester Medical Center
  • Oregon
    • Portland, Oregon, United States, 97213
      • Recruiting
      • Providence Portland Medical Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Oncology

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Documented initial diagnosis of multiple myeloma according to international myeloma working group (IMWG) diagnostic criteria
• Part 3: Measurable disease cohort A, cohort B, cohort C, and cohort D: multiple myeloma must be measurable by central laboratory assessment
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2
• Women of childbearing potential must have a negative pregnancy test at screening and prior to the first dose of study drug using a highly sensitive pregnancy test either serum (beta human chorionic gonadotropin [hCG]) or urine
• Willing and able to adhere to the prohibitions and restrictions specified in this protocol

Exclusion Criteria:

• Part 3 only: Cohort A and Cohort C only: exposed to a CAR-T or T cell redirection therapy at any time. Cohort B and Cohort D: T cell redirection therapy within 3 months
• Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy
• Received a cumulative dose of corticosteroids equivalent to >= 140 milligram (mg) of prednisone within the 14-day period before the first dose of study drug (does not include pretreatment medication)
• Stroke or seizure within 6 months prior to signing the informed consent form (ICF)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 3: Cohort A (Talquetamab); Cohort A will enroll participants with multiple myeloma who have previously received greater than or equal to (>=) 3 prior lines of therapy and have not been exposed to T cell redirection therapies. Participants will receive talquetamab subcutaneously (SC) at a recommended Phase 2 dose (RP2D) selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study.	Drug: Talquetamab; Talquetamab will be administered SC until disease progression.; Other Names: JNJ-64407564
Experimental: Part 3: Cohort B (Talquetamab); Cohort B will enroll participants with multiple myeloma who have previously received >= 3 prior lines of therapy and have been exposed to T cell redirection therapies. Participants will receive talquetamab subcutaneously (SC) at a recommended Phase 2 dose (RP2D) selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study.	Drug: Talquetamab; Talquetamab will be administered SC until disease progression.; Other Names: JNJ-64407564
Experimental: Part 3: Cohort C (Talquetamab); Cohort C will enroll participants with multiple myeloma who have previously received >= 3 prior lines of therapy and have not been exposed to T cell redirection therapies. Participants will receive talquetamab SC biweekly at a RP2D selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study.	Drug: Talquetamab; Talquetamab will be administered SC until disease progression.; Other Names: JNJ-64407564
Experimental: Part 3: Cohort D (Talquetamab); Cohort D will enroll participants with multiple myeloma who have previously received >= 3 prior lines of therapy. Participants will receive talquetamab SC biweekly at a RP2D selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study.	Drug: Talquetamab; Talquetamab will be administered SC until disease progression.; Other Names: JNJ-64407564

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	ORR is defined as the proportion of participants who have a partial response (PR) or better according to the international myeloma working group (IMWG) criteria.	Up to 2 years and 10 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response (DOR)	DOR is defined as time from date of initial documentation of a response (PR or better) to date of first documented evidence of progressive disease (PD), per IMWG criteria, or death due to PD, whichever occurs first.	Up to 2 years and 10 months
Very Good Partial Response (VGPR) or Better Rate	VGPR or better rate is defined as the percentage of patients who achieve a VGPR or better according to IMWG response criteria.	Up to 2 years and 10 months
Complete Response (CR) or Better Rate	CR or better rate is defined as the percentage of patients who achieve CR or better according to IMWG response criteria.	Up to 2 years and 10 months
Stringent Complete Response (sCR) Rate	sCR rate is defined as the percentage of patients who achieve sCR according to IMWG response criteria.	Up to 2 years and 10 months
Time to Response (TTR)	TTR is defined as the time between date of first dose of study drug and the first efficacy evaluation that the participant has met all criteria for PR or better.	Up to 2 years and 10 months
Progression-Free Survival (PFS)	PFS is defined as time from date of first dose of study drug to date of first documented PD, per IMWG criteria, or death due to any cause, whichever occurs first.	Up to 2 years and 10 months
Overall Survival (OS)	OS is defined as the time from the date of first dose of study drug to the date of the participant's death.	Up to 2 years and 10 months
Minimal Residual Disease (MRD) Negative Rate	MRD negativity rate is measured only for participants who achieve at least a CR but is reported based on all treated similar to the other response data.	Up to 2 years and 10 months
Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability	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 2 years and 10 months
Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability	An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.	Up to 2 years and 10 months
Number of Participants with AEs by Severity	Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). 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 2 years and 10 months
Number of Participants with Abnormalities in Clinical Laboratory Values	Number of participants with abnormalities in clinical laboratory values (such as hematology, serum chemistry and coagulation) will be reported.	Up to 2 years and 10 months
Serum Concentration of Talquetamab	Serum samples will be analyzed to determine concentrations of talquetamab.	Up to 2 years and 10 months
Number of Participants with Talquetamab Antibodies	Antibodies to talquetamab will be assessed to evaluate potential immunogenicity.	Up to 2 years and 10 months
Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 item (EORTC QLQ-C30)	The EORTC- QLQ-Core-30 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 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The recall period is 1 week ("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 higher score represents greater HRQoL, better functioning, and more (worse) symptoms.	Baseline up to 2 years and 10 months
Change from Baseline in HRQoL as Assessed by EuroQol Five Dimension Five Level Questionnaire (EQ-5D-5L)	The EQ-5D-5L is a generic measure of health status. 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). The scores for the 5 separate questions are categorical and cannot be analyzed as cardinal numbers.	Baseline up to 2 years and 10 months
Change from Baseline in HRQoL as Assessed by Patient Global Impression of Severity (PGIS)	The PGIS is a single item that assesses severity of the participant's health state, on a 5-point verbal rating scale. Score ranges from 1 (None) to 5 (Very Severe).	Baseline up to 2 years and 10 months
Overall Response Rate (ORR) in Participants with High-risk Molecular Features	ORR in participants with high risk is defined as the overall response rate among the high risk molecular subgroups or other high-risk molecular subtypes.	Up to 2 years and 10 months

Collaborators and Investigators

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

Publications and helpful links

Helpful Links

• Dose Escalation Study of JNJ-64407564 in Participants With Relapsed or Refractory Multiple Myeloma

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Estimated): March 31, 2026
• Study Completion (Estimated): April 13, 2026

Study Registration Dates

• First Submitted: November 16, 2020
• First Submitted That Met QC Criteria: November 16, 2020
• First Posted (Actual): November 18, 2020

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Multiple Myeloma
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms by Site; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hematologic Neoplasms; Multiple Myeloma; Neoplasms, Plasma Cell
• Other Study ID Numbers: CR108920; 2017-002400-26 (EudraCT Number); TALMMY1001-PT3 (Other Identifier: Janssen Research & Development, LLC); 2023-504581-29-00 (Registry Identifier: EUCT number)

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/clinicaltrials/ 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