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

Multiple Myeloma Clinical Trial

— MajesTEC-3  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05083169
• Other study ID #: CR109049
• Secondary ID: 2020-004742-1164
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: October 14, 2021
• Est. completion date: December 8, 2028

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

Description:

Teclistamab is a novel B-cell maturation antigen (BCMA) bispecific antibody that is being evaluated to treat participants with multiple myeloma, an incurable malignant plasma cell disorder. The primary hypothesis of this study is that Tec-Dara will significantly improve progression free survival (PFS) compared with investigator's choice of DPd/DVd in participants with relapsed refractory multiple myeloma. Approximately 560 participants will be randomly assigned in a 1:1 ratio to receive either Tec-Dara (Arm A) or investigator's choice of DPd/DVd (Arm B). The study will be conducted in 3 phases: Screening Phase, Treatment Phase, and Follow-up Phase. Participants will be treated until disease progression, unacceptable toxicity, or other reasons to discontinue the study. Disease evaluation will occur every cycle. Safety will be assessed throughout the study. Efficacy will be assessed using International Myeloma Working Group (IMWG) criteria. The overall duration of the study will be approximately 5 years.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 587
• Est. completion date: December 8, 2028
• Est. primary completion date: August 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Daratumumab
Daratumumab will be administered SC injection.
• Pomalidomide
Pomalidomide will be administered orally.
• Dexamethasone
Dexamethasone will be administered orally or intravenously.
• Bortezomib
Bortezomib will be administered SC injection.
• Teclistamab
Teclistamab will be administered SC injection.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Argentina,  Belgium,  Brazil,  Canada,  China,  Denmark,  France,  Germany,  Greece,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Poland,  Russian Federation,  Spain,  Sweden,  Taiwan,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	PFS is defined as the time from the date of randomization to the date of first documented disease progression, as defined in the International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occurs first.	Up to 5 years
Secondary	Overall Response (Partial Response [PR] or Better)	Overall response (PR or better) is defined as participants who have a PR or better per IMWG criteria.	Up to 5 years
Secondary	Very Good Partial Response (VGPR) or Better	VGPR or better is defined as participants who achieve a VGPR or better response per IMWG criteria.	Up to 5 years
Secondary	Complete Response (CR) or Better	CR or better is defined as participants who achieve a CR or better response per IMWG criteria.	Up to 5 years
Secondary	Minimal Residual Disease (MRD)-negativity	MRD-negativity is defined as participants who achieve MRD negativity at a threshold of 10^-5 at any timepoint after the date of randomization and before disease progression or start of subsequent antimyeloma therapy.	Up to 5 years
Secondary	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 on the first subsequent line of antimyeloma therapy, or death from any cause, whichever occurs first.	Up to 5 years
Secondary	Overall Survival (OS)	OS is measured from the date of randomization to the date of the participant's death.	Up to 5 years
Secondary	Time to Next Treatment (TTNT)	TTNT is defined as the interval time from randomization to the start of subsequent antimyeloma treatment.	Up to 5 years
Secondary	Duration of Response	Duration of response will be calculated among responders (with a PR or better response) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease according to the IMWG response criteria, or death due to any cause, whichever occurs first.	Up to 5 years
Secondary	Number of Participants with Adverse Events (AEs) by Severity	Number of participants with AEs by Severity will be reported.	Up to 5 years
Secondary	Serum Concentration of Teclistamab	Serum samples will be analyzed to determine concentrations of teclistamab using a validated, specific, and sensitive method.	Up to 5 years
Secondary	Number of Participants with Anti-drug Antibodies (ADAs) to Teclistamab and Daratumumab	Number of participants with ADAs to teclistamab and daratumumab will be reported.	Up to 5 years
Secondary	Time to Worsening of Symptoms	Time to worsening is measured as the interval from the date of randomization to the start date of meaningful change.	Up to 5 years
Secondary	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)	The EORTC-QLQ-C30 Version 3 includes 30 items in 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 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.	Baseline up to 5 years
Secondary	Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) Scale Score	The MySIm-Q is a disease-specific PRO assessment complementary to the EORTC-QLQ-C30. It includes 17 items resulting in a symptom subscale and an impact subscale. The recall period is the "past 7 days", and responses are reported on a 5-point verbal rating scale.	Baseline up to 5 years
Secondary	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)	The PROMIS-SD is used to assess self-reported perceptions of sleep quality, sleep depth and restoration associated with sleep. The 8-item short form will be used in this study, in which responses are scored 1 to 5 for each item. Higher overall score indicates more sleep disturbance.	Baseline up to 5 years
Secondary	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 )	The National Cancer Institute's (NCI's) PRO-CTCAE is an item library of common adverse events 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 up to 6 months
Secondary	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 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).	Baseline up to 5 years
Secondary	Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by Patient Global Impression - Severity (PGI-S)	The PGIS contains 2 questions on how the participant would currently rate severity of symptoms and impacts with a 7-day recall period. The response options are presented as a 5-point verbal rating scale from 1="none" to 5="very severe."	Baseline up to 5 years
Secondary	PFS in Participants with High-risk Molecular Features	PFS in participants with high-risk molecular features will be reported.	Up to 5 years
Secondary	Depth of Response in Participants in High-risk Molecular Features	Depth of response in participants in high-risk molecular features will be reported.	Up to 5 years