A Study of Teclistamab in Combination With Daratumumab and Lenalidomide (Tec-DR) and Talquetamab in Combination With Daratumumab and Lenalidomide (Tal-DR) in Participants With Newly Diagnosed Multiple Myeloma (MajesTEC-7)

A Phase 3 Randomized Study Comparing Teclistamab in Combination With Daratumumab SC and Lenalidomide (Tec-DR) and Talquetamab in Combination With Daratumumab SC and Lenalidomide (Tal-DR) Versus Daratumumab SC, Lenalidomide, and Dexamethasone (DRd) in Participants With Newly Diagnosed Multiple Myeloma Who Are Either Ineligible or Not Intended for Autologous Stem Cell Transplant as Initial Therapy

The purpose of this study is to compare the efficacy of teclistamab in combination with daratumumab and lenalidomide (Tec-DR) and talquetamab in combination with daratumumab and lenalidomide (Tal-DR) versus daratumumab, lenalidomide, dexamethasone (DRd).

Study Overview

• Status: Recruiting
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Lenalidomide; Drug: Teclistamab; Drug: Daratumumab; Drug: Dexamethasone; Drug: Talquetamab

Detailed Description

Teclistamab is a full-size, immunoglobin G4 proline, alanine, alanine (IgG4-PAA) bispecific antibody that targets the cluster of differentiation 3 (CD3) receptor expressed on the surface of T cells and B cell maturation antigen (BCMA). Talquetamab is a full-size, humanized IgG4-PAA bispecific antibody designed to target the CD3 receptor complex on T cells and G protein-coupled receptor class C group 5 member D (GPRC5D), which is a 7-transmembrane receptor protein that is classified as a type C G protein-coupled receptor. DRd is an approved regimen for the treatment of participants with newly diagnosed, transplant-ineligible multiple myeloma. The primary hypothesis of this study is that Tec-DR and Tal-DR will significantly improve progression free survival (PFS) or the rate of sustained minimal residual disease (MRD)-negative complete response (CR) (greater than [>]12 months) compared with DRd in participants with newly diagnosed multiple myeloma who are ineligible or not intended for autologous stem cell transplant (ASCT) as initial therapy. The study will be conducted in 3 phases: Screening, Treatment, and Follow-up. Safety Assessment includes adverse events (AEs), laboratory test results, vital sign measurements, physical examination findings, assessment of Eastern Cooperative Oncology Group (ECOG) performance status grade, and immune effector cell associated encephalopathy (ICE) score (Tec-DR and Tal-DR).

• Study Type: Interventional
• Enrollment (Estimated): 1590
• Phase: Phase 3

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

• Australia
  • Camperdown, Australia, 2050
    • Recruiting
    • Royal Prince Alfred Hospital
  • Geelong, Australia, 3220
    • Recruiting
    • Barwon Health - University Hospital Geelong
  • New South Wales, Australia, 2298
    • Recruiting
    • Calvary Mater Newcastle Hospital
  • Wollongong, Australia, 2500
    • Recruiting
    • Wollongong Hospital
  • Woolloongabba, Australia, 4102
    • Recruiting
    • Princess Alexandra Hospital
• Belgium
  • Anderlecht, Belgium, 1070
    • Recruiting
    • Institut Jules Bordet
  • Haine-Saint-Paul, La Louviere, Belgium, 7100
    • Recruiting
    • Jolimont
  • Kortrijk, Belgium, 8500
    • Recruiting
    • Az Groeninge
  • Leuven, Belgium, 3000
    • Recruiting
    • Universitair Ziekenhuis Leuven
  • Wilrijk, Belgium, 2610
    • Recruiting
    • GZA Ziekenhuizen- Campus St Augustinus
• Czechia
  • Brno - Bohunice, Czechia, 625 00
    • Recruiting
    • Fakultní Nemocnice Brno
  • Hradec Kralove, Czechia, 500 05
    • Recruiting
    • Fakultni nemocnice Hradec Kralove
  • Plzen, Czechia, 304 60
    • Recruiting
    • Fakultni nemocnice Plzen
• France
  • Creteil, France, 94010
    • Recruiting
    • APHP - Hopital Henri Mondor
  • Lille, France, 59000
    • Recruiting
    • Hôpital Claude Huriez
  • Nantes, France, 44093
    • Recruiting
    • CHU Nantes
  • Pessac cedex, France, 33604
    • Recruiting
    • CHU de Bordeaux - Hospital Haut-Leveque
  • Pierre-Benite, France, 69310
    • Recruiting
    • CHU Lyon Sud
  • Toulouse, France, 31000
    • Recruiting
    • Institut Universitaire du Cancer Toulouse Oncopole
• Germany
  • Nuernberg, Germany, 90419
    • Recruiting
    • Klinikum Nuernberg Nord
• Italy
  • Bologna, Italy, 40138
    • Recruiting
    • A O U Sant Orsola Malpighi
  • Milan, Italy, 20132
    • Recruiting
    • Ospedale San Raffaele
  • Pavia, Italy, 27100
    • Recruiting
    • IRCCS Policlinico San Matteo, Università degli studi di Pavi
  • Rozzano, Italy, 20089
    • Recruiting
    • Istituto Clinico Humanitas
  • Torino, Italy, 10126
    • Recruiting
    • Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino
• Korea, Republic of
  • Busan, Korea, Republic of, 49241
    • Recruiting
    • Pusan National University Hospital
  • Goyang si, Korea, Republic of, 10408
    • Recruiting
    • National Cancer Center
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • Recruiting
    • VUMC Amsterdam
  • Apeldoorn, Netherlands, 7334 DZ
    • Recruiting
    • Gelre Ziekenhuis
  • Nieuwegein, Netherlands, 3435 CM
    • Recruiting
    • St. Antonius Ziekenhuis Nieuwegein
• Poland
  • Katowice, Poland, 40-519
    • Recruiting
    • Pratia Onkologia Katowice
  • Kielce, Poland, 25-734
    • Recruiting
    • Swietokrzyskie Centrum Onkologii SPZOZ w Kielcach
• Spain
  • Granada, Spain, 18014
    • Recruiting
    • Hosp. Univ. Virgen de Las Nieves
  • Madrid, Spain, 28041
    • Recruiting
    • Hosp. Univ. 12 de Octubre
  • Madrid, Spain, 28046
    • Recruiting
    • Hosp. Univ. La Paz
  • Madrid, Spain, 28050
    • Recruiting
    • Hosp. Univ. Hm Sanchinarro
  • Palma de Mallorca, Spain, 07120
    • Recruiting
    • Hosp. Univ. Son Espases
  • Salamanca, Spain, 37007
    • Recruiting
    • Hosp. Clinico Univ. de Salamanca
  • Terrassa, Spain, 08221
    • Recruiting
    • Hosp. Mutua Terrassa
  • Valencia, Spain, 46010
    • Recruiting
    • Hosp. Clinico Univ. de Valencia
• Sweden
  • Falun, Sweden, 791 82
    • Recruiting
    • Falu Lasarett
  • Lund, Sweden, 221 85
    • Recruiting
    • Skånes universitetssjukhus
  • Stockholm, Sweden, 141 86
    • Recruiting
    • Karolinska University Hospital, Huddinge
  • Örebro, Sweden, 701 85
    • Recruiting
    • Universitetssjukhuset Örebro
• Switzerland
  • Bern, Switzerland, 3010
    • Recruiting
    • Inselspital, Universitätsspital Bern
  • St. Gallen, Switzerland, 9007
    • Recruiting
    • Kantonsspital St.Gallen
• Turkey
  • Ankara, Turkey, 06590
    • Recruiting
    • Ankara University Medical Faculty
  • Izmir, Turkey, 35340
    • Completed
    • Dokuz Eylul University Medical Faculty
  • Samsun, Turkey, 55280
    • Recruiting
    • Ondokuz Mayis University
• United Kingdom
  • Blackpool, United Kingdom, FY3 8NR
    • Recruiting
    • Blackpool Victoria Hospital
  • Canterbury, United Kingdom, CT1 3NG
    • Recruiting
    • Kent and Canterbury Hospital
  • Edinburgh, United Kingdom, EH4 2XU
    • Recruiting
    • Western General Hospital
  • London, United Kingdom, W2 1NY
    • Recruiting
    • Imperial College Healthcare

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Have a diagnosis of multiple myeloma according to the International Myeloma Working Group (IMWG) diagnostic criteria
• Be newly diagnosed and not considered a candidate for high-dose chemotherapy with autologous stem cell transplant (ASCT) due to: ineligible due to advanced age OR; ineligible due to the presence of comorbid condition(s) likely to have a negative impact on tolerability of high-dose chemotherapy with ASCT OR; deferral of high-dose chemotherapy with ASCT as initial treatment
• Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2
• A participant must agree not to be pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of study treatment
• A participant must agree not to plan to father a child while enrolled in this study or within 100 days after the last dose of study treatment

Exclusion Criteria:

• Received any prior therapy for multiple myeloma or smoldering myeloma other than a short course of corticosteroids (not to exceed 40 milligrams [mg] of dexamethasone, or equivalent per day for a maximum of 4 days, total of 160 mg dexamethasone or equivalent). In addition, received a cumulative dose of systemic corticosteroids equivalent to greater than or equals to (>=)20 mg of dexamethasone during the Screening Phase
• Had plasmapheresis within 28 days of randomization
• Had a stroke, transient ischemic attack, or seizure within 6 months prior to randomization
• Known allergies, hypersensitivity, or intolerance to teclistamab or talquetamab excipients
• Known contraindications to the use of daratumumab or lenalidomide per local prescribing information
• Myeloma Frailty Index of >=2 with the exception of participants who have a score of 2 based on age alone

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Teclistamab, Daratumumab SC, and Lenalidomide (Tec-DR); Participants will receive teclistamab as subcutaneous (SC) injection in combination with daratumumab and lenalidomide.	Drug: Lenalidomide; Lenalidomide will be administered orally.; Drug: Teclistamab; Teclistamab will be administered as SC injection.; Other Names: JNJ-64007957; Drug: Daratumumab; Daratumumab will be administered as SC injection.
Experimental: Talquetamab, Daratumumab SC, and Lenalidomide (Tal-DR); Participants will receive talquetamab as SC injection in combination with daratumumab and lenalidomide.	Drug: Lenalidomide; Lenalidomide will be administered orally.; Drug: Daratumumab; Daratumumab will be administered as SC injection.; Drug: Talquetamab; Talquetamab will be administered as SC injection.; Other Names: JNJ-64407564
Active Comparator: Daratumumab SC, Lenalidomide, and Dexamethasone (DRd); Participants will receive daratumumab as SC injection with lenalidomide and dexamethasone.	Drug: Lenalidomide; Lenalidomide will be administered orally.; Drug: Daratumumab; Daratumumab will be administered as SC injection.; Drug: Dexamethasone; Dexamethasone will be administered either orally or intravenously (IV).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS)	PFS is defined as the duration from the date of randomization to either progressive disease or death, whichever comes first. Disease progression will be determined according to the International Myeloma Working Group (IMWG) response criteria.	From randomization to the date of disease progression or death (Up to 9 years)
Complete Response (CR) or Better	CR or better is defined as the percentage of participants achieving CR or stringent complete response (sCR) prior to subsequent antimyeloma therapy in accordance with the IMWG criteria during or after the study treatment.	From randomization up to 9 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Very Good Partial Response (VGPR) or Better	VGPR or better is defined as the percentage of participants achieving VGPR and CR (including sCR) prior to subsequent antimyeloma therapy in accordance with the IMWG criteria during or after the study treatment.	From randomization up to 9 years
Sustained Minimal Residual disease (MRD)-negative Complete Response (CR)	Sustained MRD-negative CR is defined as participants with CR or better who sustain MRD-negative status, as determined by next-generation sequencing (NGS) with sensitivity of 10^-5, for at least 12 months without any examination showing MRD positive status or progressive disease in between.	From randomization up to 9 years
MRD-negative CR	MRD-negative CR is defined as the percentage of participants who achieve MRD-negative status, as determined by NGS with sensitivity of 10^-5, at any time after randomization and prior to progressive disease or subsequent antimyeloma therapy and who achieve CR or better.	From randomization up to 9 years
Progression Free Survival on Next-line Therapy (PFS2)	PFS2 is defined as the time interval between the date of randomization and date of event, which is defined as progressive disease as assessed by investigator that starts after the next line of subsequent therapy, or death from any cause, whichever occurs first.	From randomization up to 9 years
Overall Survival (OS)	OS is defined as the time from the date of randomization to the date of death due to any cause.	From randomization to the date of death (up to 9 years)
Number of Participants with Adverse Events (AEs) by Severity	An adverse event is any untoward medical occurrence in a clinical study participant administered a pharmaceutical (investigational or non-investigational) product. An adverse event does not necessarily have a causal relationship with the treatment. 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, Grade 2: moderate, Grade 3: severe, Grade 4: life-threatening, and Grade 5: death related to adverse event.	From randomization up to 9 years
Number of Participants with Abnormalities in Laboratory Parameters	Number of participants with abnormalities in laboratory parameters (serum chemistry and hematology) will be reported.	From randomization up to 9 years
Number of Participants with Abnormalities in Vital Signs	Number of participants with abnormalities in vital signs (temperature, pulse/heart rate, respiratory rate, blood pressure) will be reported.	From randomization up to 9 years
Number of Participants with Abnormalities in Physical Examination	Number of participants with abnormalities in physical examination will be reported.	From randomization up to 9 years
Number of Participants with Abnormalities in Electrocardiogram (ECG)	Number of participants with abnormalities in ECG will be reported.	From randomization up to 9 years
Serum Concentrations of Teclistamab and Talquetamab	Serum samples will be analyzed to determine concentrations of teclistamab and talquetamab using validated, specific, and sensitive methods.	From randomization up to 9 years
Number of Participants with Anti-drug Antibodies (ADAs) to Teclistamab and Talquetamab	Number of participants with ADAs to teclistamab and talquetamab will be reported.	From randomization up to 9 years
Change from Baseline in Symptoms, Functioning, and Health-related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (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. Thus, a high score for a functional scale represents a high/healthy level of functioning and a high score for the global health status represents high HRQoL, but a high score for a symptom scale/item represents a high level of symptomatology/problems.	From baseline up to 9 years
Change from Baseline in Treatment-related Symptoms as Assessed by Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE)	The National Cancer Institute's (NCI's) PRO-CTCAE is an item library of common AEs experienced by people with cancer that are appropriate for self-reporting of treatment tolerability. Each symptom selected for inclusion can be rated by up to 3 attributes characterizing the presence/frequency, severity, and/or interference of the AEs. It ranges from 0 to 4 with higher scores indicating higher frequency or greater severity/impact.	Baseline through Cycle 6 (each cycle of 28 days) (up to 196 days)
Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by EuroQol Five Dimension Questionnaire 5-Level (EQ-5D-5L)	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).	From baseline up to 9 years
Time to Sustained Worsening in Symptoms, Functioning, and HRQoL	Time to sustained worsening in symptoms, functioning and HRQoL is defined as the interval from the date of randomization to the start date of meaningful change.	From randomization up to 9 years

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): October 25, 2022
• Primary Completion (Estimated): April 30, 2031
• Study Completion (Estimated): August 29, 2033

Study Registration Dates

• First Submitted: September 21, 2022
• First Submitted That Met QC Criteria: September 21, 2022
• First Posted (Actual): September 23, 2022

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

• 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; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Dexamethasone; Lenalidomide; Daratumumab
• Other Study ID Numbers: CR109237; 64007957MMY3005 (Other Identifier: Janssen Research & Development, LLC); 2022-000909-28 (EudraCT Number); 2023-503442-30-00 (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/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