Clinical trial NCT05083169: A Study of Teclistamab in Combination With Daratumumab Subcutaneously (SC) (Tec-Dara) Versus Daratumumab SC, Pomalidomide, and Dexamethasone (DPd) or Daratumumab SC, Bortezomib, and Dexamethasone (DVd) in Participants With Relapsed or Refractory Multiple Myeloma
Official title: A Phase 3 Randomized Study Comparing Teclistamab in Combination With Daratumumab SC (Tec-Dara) Versus Daratumumab SC, Pomalidomide, and Dexamethasone (DPd) or Daratumumab SC, Bortezomib, and Dexamethasone (DVd) in Participants With Relapsed or Refractory Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Multiple Myeloma
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2021-10-19
Enrollment: 587
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to compare the efficacy of teclistamab daratumumab (Tec-Dara) with daratumumab subcutaneously (SC) in combination with pomalidomide and dexamethasone (DPd) or daratumumab SC in combination with bortezomib and dexamethasone (DVd).


Eligibility criteria: Inclusion Criteria:

* Documented multiple myeloma as defined by the criteria: a. multiple myeloma diagnosis according to the International Myeloma Working Group (IMWG) diagnostic criteria, b. measurable disease at screening as defined by any of the following: 1) serum M-protein level greater than or equal to (\>=) 0.5 gram per deciliter (g/dL); or 2) urine M-protein level \>=200 milligrams (mg)/24 hours; or 3) serum immunoglobulin free light chain \>=10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio
* Received 1 to 3 prior line(s) of antimyeloma therapy including a proteasome inhibitor (PI) and lenalidomide; a. participants who have received only 1 line of prior line of antimyeloma therapy must be lenalidomide refractory. Stable disease or progression on or within 60 days of the last dose of lenalidomide given as maintenance will meet this criterion
* 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 score of 0, 1, or 2 at screening and prior to the start of administration of study treatment
* Have clinical laboratory values within the specified range

Exclusion Criteria:

* Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients. Additional exclusion criteria pertaining to specific study drugs include:

  1. A participant is not eligible to receive daratumumab subcutaneous (SC) in combination with pomalidomide and dexamethasone (DPd) as control therapy if any of the following are present: 1) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to pomalidomide, 2) Disease that is considered refractory to pomalidomide per IMWG,
  2. A participant is not eligible to receive daratumumab SC in combination with bortezomib and dexamethasone (DVd) as control therapy if any of the following are present: 1) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to bortezomib, 2) Grade 1 peripheral neuropathy with pain or Grade \>= 2 peripheral neuropathy as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0, 3) Disease that is considered refractory to bortezomib per IMWG, 4) Received a strong cytochromes P450 (CYP3A4) inducer within 5 half-lives prior to randomization
* Received any prior B cell maturation antigen (BCMA)-directed therapy
* Has disease that is considered refractory to an anti-cluster of differentiation 38 (CD38) monoclonal antibody per IMWG
* Received a cumulative dose of corticosteroids equivalent to \>=140 mg of prednisone within 14 days before randomization
* Received a live, attenuated vaccine within 4 weeks before randomization
* Plasma cell leukemia at the time of screening, Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), or primary amyloid light chain amyloidosis

Primary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: Up to 5 years
Secondary outcomes:
measure: Overall Response (Partial Response [PR] or Better)
timeFrame: Up to 5 years
measure: Very Good Partial Response (VGPR) or Better
timeFrame: Up to 5 years
measure: Complete Response (CR) or Better
timeFrame: Up to 5 years
measure: Minimal Residual Disease (MRD)-negativity
timeFrame: Up to 5 years
measure: Progression Free Survival on Next-line Therapy (PFS2)
timeFrame: Up to 5 years
measure: Overall Survival (OS)
timeFrame: Up to 5 years
measure: Time to Next Treatment (TTNT)
timeFrame: Up to 5 years
measure: Duration of Response
timeFrame: Up to 5 years
measure: Number of Participants with Adverse Events (AEs) by Severity
timeFrame: Up to 5 years
measure: Serum Concentration of Teclistamab
timeFrame: Up to 5 years
measure: Number of Participants with Anti-drug Antibodies (ADAs) to Teclistamab and Daratumumab
timeFrame: Up to 5 years
measure: Time to Worsening of Symptoms
timeFrame: Up to 5 years
measure: Change from Baseline in Symptoms, Functioning, and Overall 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)
timeFrame: Baseline up to 5 years
measure: Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) Scale Score
timeFrame: Baseline up to 5 years
measure: Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by Patient-reported Outcomes Measurement Information System Short Form v2.0 - Physical Function 8c (PROMIS PF 8c)
timeFrame: Baseline up to 5 years
measure: Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by Patient-reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE )
timeFrame: Baseline up to 6 months
measure: Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by EuroQol Five Dimension Questionnaire 5-Level (EQ-5D-5L)
timeFrame: Baseline up to 5 years
measure: Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by Patient Global Impression - Severity (PGI-S)
timeFrame: Baseline up to 5 years
measure: PFS in Participants with High-risk Molecular Features
timeFrame: Up to 5 years
measure: Depth of Response in Participants in High-risk Molecular Features
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama Birmingham
state: Alabama
city: Duarte
country: United States
facility: City of Hope
state: California
city: Stanford
country: United States
facility: Stanford University Medical Center
state: California
city: New Haven
country: United States
facility: Yale University
state: Connecticut
city: Atlanta
country: United States
facility: Emory University Winship Cancer Institute
state: Georgia
city: Boston
country: United States
facility: Tufts Medical Center
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Hospital
state: Michigan
city: Southfield
country: United States
facility: Ascension Providence Hospital
state: Michigan
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Pittsburgh
country: United States
facility: West Penn Hospital
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Memphis
country: United States
facility: Baptist Cancer Center
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt Ingram Cancer Center
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
city: Buenos Aires
country: Argentina
facility: Hospital Aleman
city: Buenos Aires
country: Argentina
facility: Hospital Italiano de Buenos Aires
city: Cordoba
country: Argentina
facility: Hospital Privado Centro Medico de Cordoba
city: Antwerpen
country: Belgium
facility: ZNA Cadix
city: Brugge
country: Belgium
facility: AZ St.-Jan Brugge-Oostende AV
city: Gent
country: Belgium
facility: UZ Gent
city: Haine Saint Paul La Louviere
country: Belgium
facility: Hopital de Jolimont
city: Kortrijk
country: Belgium
facility: Az Groeninge
city: Leuven
country: Belgium
facility: UZ Leuven
city: Roeselare
country: Belgium
facility: Algemeen Ziekenhuis Delta
city: Brasilia
country: Brazil
facility: Hospitais Integradaos da Gavea S/A - DF Star
city: Curitiba
country: Brazil
facility: Liga Paranaense de Combate ao Cancer
city: Florianopolis
country: Brazil
facility: Centro de Pesquisa e Ensino em Oncologia de Santa Catarina CEPEN
city: Natal
country: Brazil
facility: Liga Norte Riograndense Contra O Cancer
city: Porto Alegre
country: Brazil
facility: Irmandade Santa Casa de Misericordia de Porto Alegre
city: Rio de Janeiro
country: Brazil
facility: Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)
city: Salvador
country: Brazil
facility: Hospital Sao Rafael
city: Sao Paulo
country: Brazil
facility: Real e Benemerita Associacao Portuguesa de Beneficencia
city: Sao Paulo
country: Brazil
facility: Hospital Paulistano
city: Sao Paulo
country: Brazil
facility: Clinica Medica Sao Germano S/S LTDA
city: São Paulo
country: Brazil
facility: Instituto D Or de Pesquisa e Ensino IDOR
city: Calgary
country: Canada
facility: Arthur J E Child Comprehensive Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Vancouver
country: Canada
facility: BC Cancer Agency - Vancouver BC
state: British Columbia
city: Halifax
country: Canada
facility: QEII Health Sciences
state: Nova Scotia
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre University Health Network
state: Ontario
city: Beijing
country: China
facility: Peking University First Hospital
city: Beijing
country: China
facility: Peking University People s Hospital
city: Beijing
country: China
facility: Peking University Third Hospital
city: Changchun
country: China
facility: The First Hospital of Jilin University
city: Changshashi
country: China
facility: The Third Xiangya Hospital of Central Sourth University
city: Chaoyang District
country: China
facility: Beijing Chaoyang Hospital
city: Chengdu
country: China
facility: West China Hospital Sichuan University
city: Fuzhou
country: China
facility: Fujian Meidical University Union Hospital
city: Guangzhou
country: China
facility: Sun Yat Sen University Cancer Center
city: Hangzhou
country: China
facility: First affiliated Hospital of Zhejiang University
city: Nanjing
country: China
facility: Zhongda Hospital Southeast University
city: Nanning
country: China
facility: First Affiliated Hospital of Guangxi Medical University
city: Shanghai
country: China
facility: Shanghai Zhongshan Hospital
city: Shenyang
country: China
facility: Shengjing Hospital Of China Medical University
city: Shenzhen
country: China
facility: Peking University Shenzhen Hospital
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
city: Tianjin
country: China
facility: Tianjin Medical University Cancer Institute and Hospital
city: Xi'an
country: China
facility: The Second Affiliated Hospital of Xi'an Jiaotong University
city: Xuzhou
country: China
facility: The Affiliated Hospital of Xuzhou Medical University
city: Zhengzhou
country: China
facility: Henan Cancer Hospital
city: Aalborg
country: Denmark
facility: Aalborg University Hospital
city: Aarhus N
country: Denmark
facility: Aarhus University Hospital
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Odense
country: Denmark
facility: Odense Universitets Hospital
city: Vejle
country: Denmark
facility: Vejle Hospital
city: Creteil
country: France
facility: CHU Henri Mondor
city: LILLE Cedex
country: France
facility: CHRU de Lille Hopital Claude Huriez
city: Limoges
country: France
facility: CHU de Limoges Hopital Dupuytren
city: Nantes
country: France
facility: C.H.U. Hotel Dieu - France
city: Pierre Benite cedex
country: France
facility: Centre hospitalier Lyon-Sud
city: Poitiers
country: France
facility: CHU De Poitiers
city: Strasbourg
country: France
facility: Institut de Cancerologie Strasbourg Europe ICANS
city: Toulouse cedex 9
country: France
facility: Pôle IUC Oncopole CHU
city: Tours
country: France
facility: CHRU Hôpital Bretonneau
city: Dresden
country: Germany
facility: Universitätsklinikum Carl-Gustav-Carus Dresden
city: Düsseldorf
country: Germany
facility: Heinrich-Heine -Universitaet Duesseldorf
city: Essen
country: Germany
facility: Evang. Krankenhaus Essen-Mitte gGmbH
city: Freiburg
country: Germany
facility: Universitatsklinikum Freiburg
city: Hamburg
country: Germany
facility: Universitaetsklinikum Hamburg Eppendorf
city: Hamm
country: Germany
facility: St. Barbara-Klinik Hamm GmbH
city: Heidelberg
country: Germany
facility: Universitaetsklinikum Heidelberg
city: Kiel
country: Germany
facility: Universitaetsklinikum Schleswig Holstein Campus Kiel
city: Leipzig
country: Germany
facility: Universitaetsklinikum Leipzig
city: Tubingen
country: Germany
facility: Universitaetsklinikum Tuebingen
city: Athens Attica
country: Greece
facility: Alexandra General Hospital of Athens
city: Thessaloniki
country: Greece
facility: Anticancer Hospital of Thessaloniki Theageneio
city: Thessaloniki
country: Greece
facility: G.Papanikolaou
city: Bari
country: Italy
facility: U.O. Ematologia con Trapianto- AOU Policlinico di Bari
city: Bergamo
country: Italy
facility: ASST Papa Giovanni XXIII Bergamo
city: Bologna
country: Italy
facility: Policlinico Sant'Orsola Malpighi
city: Firenze
country: Italy
facility: Azienda Ospedaliera Universitaria Careggi
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
city: Pavia
country: Italy
facility: IRCCS Policlinico San Matteo, Università degli studi di Pavi
city: Roma
country: Italy
facility: Università di Roma 'La Sapienza' - Ospedale Umberto 1°
city: Turin
country: Italy
facility: A.O.U. Citta della Salute e della Scienza di Torino - Presidio Molinette
city: Fukuoka
country: Japan
facility: Fukuoka University Hospital
city: Gifu
country: Japan
facility: Ogaki Municipal Hospital
city: Higashiibaraki-gun
country: Japan
facility: National Hospital Organization Mito Medical Center
city: Isehara
country: Japan
facility: Tokai University Hospital
city: Kamakura-shi
country: Japan
facility: Shonan Kamakura General Hospital
city: Kashiwa
country: Japan
facility: National Cancer Center Hospital East
city: Koshigaya
country: Japan
facility: Dokkyo Medical University Saitama Medical Center
city: Kumamoto
country: Japan
facility: Kumamoto University Hospital
city: Kurume
country: Japan
facility: Kurume University Hospital
city: Matsumoto
country: Japan
facility: National Hospital Organization Matsumoto Medical Center
city: Nagoya
country: Japan
facility: Nagoya City University Hospital
city: Nishinomiya shi
country: Japan
facility: Hyogo Medical University Hospital
city: Okayama
country: Japan
facility: National Hospital Organization Okayama Medical Center
city: Otake
country: Japan
facility: National Hospital Organization Hiroshima-Nishi Medical Center
city: Sapporo-shi
country: Japan
facility: Hokkaido University Hospital
city: Sendai-City
country: Japan
facility: National Hospital Organization Sendai Medical Center
city: Sendai
country: Japan
facility: Tohoku University Hospital
city: Shibuya-ku
country: Japan
facility: Japanese Red Cross Medical Center
city: Shiwa-gun
country: Japan
facility: Iwate Medical University Hospital
city: Daegu
country: Korea, Republic of
facility: Kyungpook National University Hospital
city: Incheon
country: Korea, Republic of
facility: Gachon University Gil Medical Center
city: Jeollanam-do
country: Korea, Republic of
facility: Chonnam National University Hwasun Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St Marys Hospital
city: Amsterdam
country: Netherlands
facility: VU Medisch Centrum
city: Groningen
country: Netherlands
facility: Universitair Medisch Centrum Groningen
city: Nieuwegein
country: Netherlands
facility: Sint Antonius Ziekenhuis - Afd.Interne - INT
city: Nijmegen
country: Netherlands
facility: Radboudumc
city: Zwolle
country: Netherlands
facility: Isala Kliniek
city: Gdansk
country: Poland
facility: Klinika Hematologii i Transplantologii, UCK
city: Katowice
country: Poland
facility: Pratia Onkologia Katowice
city: Kielce
country: Poland
facility: Swietokrzyskie Centrum Onkologii SPZOZ w Kielcach
city: Lublin
country: Poland
facility: Centrum Onkologii Ziemi Lubelskiej im sw Jana z Dukli
city: Walbrzych
country: Poland
facility: Specjalistyczny Szpital im dra Alfreda Sokolowskiego w Walbrzychu
city: Warszawa
country: Poland
facility: Narodowy Instytut Onkologii im Marii Sklodowskiej Curie Panstwowy Instytut Badawczy
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny im Jana Mikulicza Radeckiego we Wroclawiu
city: Moscow
country: Russian Federation
facility: S.P. Botkin Moscow City Clinical Hospital
city: St-Petersburg
country: Russian Federation
facility: Clinical Research Institute of Hematology and Transfusiology
city: Barcelona
country: Spain
facility: Inst. Cat. Doncologia-H Duran I Reynals
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Gijón
country: Spain
facility: Hosp. de Cabuenes
city: Las Palmas de Gran Canaria
country: Spain
facility: Hosp. Univ. de Gran Canaria Dr. Negrin
city: Madrid
country: Spain
facility: Hosp. Gral. Univ. Gregorio Maranon
city: Madrid
country: Spain
facility: Hosp. Univ. Ramon Y Cajal
city: Madrid
country: Spain
facility: Hosp. Univ. 12 de Octubre
city: Palma
country: Spain
facility: Hosp. Univ. Son Espases
city: Pamplona
country: Spain
facility: Clinica Univ. de Navarra
city: Pozuelo de Alarcon
country: Spain
facility: Hosp. Quiron Madrid Pozuelo
city: Salamanca
country: Spain
facility: Hosp Clinico Univ de Salamanca
city: Santander
country: Spain
facility: Hosp. Univ. Marques de Valdecilla
city: Santiago de Compostela
country: Spain
facility: Hosp. Clinico Univ. de Santiago
city: Sevilla
country: Spain
facility: Hosp. Virgen Del Rocio
city: Valencia
country: Spain
facility: Hosp. Univ. I Politecni La Fe
city: Falun
country: Sweden
facility: Falu Lasarett
city: Göteborg
country: Sweden
facility: Sahlgrenska University Hospital
city: Helsingborg
country: Sweden
facility: Helsingborgs lasarett
city: Luleå
country: Sweden
facility: Sunderby Sjukhus
city: Lund
country: Sweden
facility: Skanes universitetssjukhus
city: Umea
country: Sweden
facility: Norrlands Universitetssjukhus
city: Uppsala
country: Sweden
facility: Akademiska Sjukhuset
city: Taichung
country: Taiwan
facility: China Medical University Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital
city: Ankara
country: Turkey
facility: Ankara University Medical Faculty
city: Atakum
country: Turkey
facility: Ondokuz Mayis University
city: Istanbul
country: Turkey
facility: Medipol University Hospital
city: Izmir
country: Turkey
facility: Dokuz Eylul University Medical Faculty
city: Blackpool
country: United Kingdom
facility: Blackpool Teaching Hospitals NHS Foundation Trust
city: Dundee
country: United Kingdom
facility: Ninewells Hospital & Medical School
city: London
country: United Kingdom
facility: Kings College Hospital
city: Oxford
country: United Kingdom
facility: Oxford University Hospitals NHS Foundation Trust
city: Plymouth
country: United Kingdom
facility: University Hospitals Plymouth NHS Trust
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trial
role: STUDY_DIRECTOR
References: