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).

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

Multiple Myeloma

Kahler's Disease

Blood Cancer

Hematologic Neoplasms

Hematologic Malignancies

Hematology

Hematological Malignancies

Daratumumab

Lenalidomide

Dexamethasone

Teclistamab

Talquetamab

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

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.

12-month MRD-negative CR is defined as participants who achieve MRD-negative status at 12 months, as determined by next-generation sequencing (NGS) with sensitivity of 10^-5, prior to progressive disease or subsequent anti-myeloma therapy and who also achieve CR or better, according to IMWG criteria.

VGPR or better is defined as the percentage of participants achieving VGPR and CR (including stringent complete response [sCR]) prior to subsequent antimyeloma therapy in accordance with the IMWG criteria during or after the study treatment.

CR or better is defined as the percentage of participants achieving CR or sCR prior to subsequent antimyeloma therapy in accordance with the IMWG criteria during or after the study treatment.

Sustained MRD-negative CR is defined as participants with CR or better who sustain MRD-negative status, as determined by NGS with sensitivity of 10^-5, for at least 12 months without any examination showing MRD positive status or progressive disease in between.

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.

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.

OS is defined as the time from the date of randomization to the date of death due to any cause.

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.

Number of participants with abnormalities in laboratory parameters (serum chemistry and hematology) will be reported.

Number of participants with abnormalities in vital signs (temperature, pulse/heart rate, respiratory rate, blood pressure) will be reported.

Number of participants with abnormalities in physical examination will be reported.

Number of participants with abnormalities in ECG will be reported.

Serum samples will be analyzed to determine concentrations of teclistamab and talquetamab using validated, specific, and sensitive methods.

Number of participants with ADAs to teclistamab and talquetamab will be reported.

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.

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.

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).

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.

Participants will receive teclistamab as subcutaneous (SC) injection in combination with daratumumab and lenalidomide.

Participants will receive talquetamab as SC injection in combination with daratumumab and lenalidomide.

Participants will receive daratumumab as SC injection with lenalidomide and dexamethasone.

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).

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).

Barwon Health - University Hospital Geelong

Calvary Mater Newcastle Hospital

Wollongong Hospital

Institut Jules Bordet

Jolimont

Az Groeninge

Universitair Ziekenhuis Leuven

GZA Ziekenhuizen- Campus St Augustinus

Fakultni nemocnice Hradec Kralove

Fakultni nemocnice Plzen

APHP - Hopital Henri Mondor

Hopital Claude Huriez

CHU Nantes

CHU de Bordeaux - Hospital Haut-Leveque

CHU Lyon Sud

Institut Universitaire du Cancer Toulouse Oncopole

A.O.U Sant'Orsola-Malpighi

Ospedale San Raffaele

IRCCS Policlinico San Matteo, Università degli studi di Pavi

Istituto Clinico Humanitas

Azienda Ospedaliera Universitaria Città della Salute e della Scienza di Torino

Gelre Ziekenhuis

St. Antonius Ziekenhuis Nieuwegein

Pratia Onkologia Katowice

Swietokrzyskie Centrum Onkologii SPZOZ w Kielcach

Hosp. Univ. Virgen de Las Nieves

Hosp. Univ. 12 de Octubre

Hosp. Univ. La Paz

Hosp. Univ. Hm Sanchinarro

Hosp. Univ. Son Espases

Hosp. Clinico Univ. de Salamanca

Hosp. Mutua Terrassa

Falu Lasarett

Skanes universitetssjukhus

Karolinska University Hospital, Huddinge

Universitetssjukhuset Orebro

Ankara University Medical Faculty

Kent and Canterbury Hospital

Imperial College Healthcare

PFS is defined as the duration from the date of randomization to either progressive disease or death, whichever comes first.

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.

VGPR or better is defined as the percentage of participants achieving VGPR and CR (including stringent complete response [sCR]) prior to subsequent antimyeloma therapy in accordance with the International Myeloma Working Group (IMWG) criteria during or after the study treatment.

Henry Ford Cancer - Detroit Brigitte Harris Cancer Pavilion

Henry Ford Providence Novi Hospital

Dartmouth Hitchcock Medical Center

Astera Cancer Care

Hematology-Oncology Associates of CNY

Northwell Health Cancer Institute

Perlmutter Cancer Center at NYU Langone Health

OhioHealth

Allegheny Health Network

Henry-Joyce Cancer Clinic

Cleveland Clinic Florida

City of Hope Cancer Center

University Of Illinois Medical Center

University of Iowa Health Care

University of Michigan

Cancer And Hematology Centers of Western Michigan PC

MidAmerica Cancer Care

Novant Health Zimmer Cancer Institute

Novant Health Forsyth Medical Center

MUSC-Hollings Cancer Center

University of Texas Southwestern Medical Center

Houston Methodist Hospital

Joe Arrington Cancer Research Treatment Center

Utah Cancer Specialists

Alexander T. Augusta Military Medical Center

Richmond VA Medical Center

NorthWest Medical Specialties, PLLC

Princess Alexandra Hospital

Ordensklinikum Linz GmbH Elisabethinen

SCRI CCCIT gem GmbH

Shanghai Fourth People s Hospital

Shengjing Hospital Of China Medical University

Yamagata University Hospital

Seoul National University Hospital

Kantonsspital St Gallen

Dokuz Eylul University Medical Faculty

Western General Hospital

University College London Hospitals

Shaare Zedek Medical Center

Rabin

Sheba Medical Center

Tel Aviv Sourasky Medical Center

ASST Papa Giovanni XXIII Bergamo

A O U Sant Orsola Malpighi

Careggi University Hospital

Asan Medical Center

University of Connecticut

Yale New Haven Hospital

Memorial Healthcare System

ZAS Augustinus

Hospital Nove de Julho

CHU Hopital Saint Antoine

Hôpitaux Universitaires de Strasbourg - Hôpital de Hautepierre

Osaka Metropolitan University Hospital

Uniwersytecki Szpital Kliniczny w Poznaniu

Banner MD Anderson Cancer Center

Cancer and Blood Specialty Clinic

Valkyrie Clinical Trials

ChristianaCare Helen F Graham Cancer Center and Research Institute

Norton Cancer Institute

Center for Cancer and Blood Disorders

Henry Ford Providence Southfield CK Potluri Cancer Center

Nebraska Cancer Specialists

University of Nebraska Medical Center

Christus St. Vincent Regional Cancer Center

NYU Langone Hospital Long Island

Memorial Sloan Kettering Cancer Center

Weill Cornell Medical College

Levine Cancer Institute

Atrium Health Wake Forest Baptist Comprehensive Cancer Center

Oncology Hematology Care

University of Cincinnati

University Hospitals Cleveland Medical Center

Cleveland Clinic Main Campus

The Ohio State University- James Cancer Hospital

Rhode Island Hospital

Huntsman Cancer Institute

University of Virginia

Virginia Oncology Associates Brock Cancer Center

Virginia Commonwealth University Medical Center

Royal Prince Alfred Hospital

Medical University Vienna

Hanusch Krankenhaus

ZAS Cadix

Ghent University Hospital

Fundacao Pio XII

Santa Casa de Misericordia de Belo Horizonte

Hospital Sao Rafael

Liga Paranaense de Combate ao Cancer

Clinica Medica Sao Germano S/S LTDA

Lakeridge Health Oshawa

CHU de Quebec L Hotel Dieu de Quebec

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

Trials at a glance

Trials at a glance

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

Outcome measures

Primary outcome measures

Secondary outcome measures