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 Clinical Trial

— MajesTEC-7  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05552222
• Other study ID #: CR109237
• Secondary ID: 64007957MMY30052
• Status: Recruiting
• Phase: Phase 3
• Start date: October 25, 2022
• Est. completion date: October 28, 2033

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: Study Contact
• Phone: 844-434-4210
• Email: Participate-In-This-Study[@]its.jnj.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 1590
• Est. completion date: October 28, 2033
• Est. primary completion date: April 30, 2031
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 total of 160 milligrams [mg] dexamethasone or equivalent). In addition, received a cumulative dose of systemic corticosteroids equivalent to greater than or equals to (>=) 20 mg of dexamethasone within 14 days before randomization
• 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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Teclistamab
Teclistamab will be administered as SC injection.
• Daratumumab
Daratumumab will be administered as SC injection.
• Lenalidomide
Lenalidomide will be administered orally.
• Dexamethasone
Dexamethasone will be administered either orally or intravenously (IV).
• Talquetamab
Talquetamab will be administered as SC injection.

Locations

Country	Name	City	State
Australia	Royal Prince Alfred Hospital	Camperdown
Australia	Barwon Health - University Hospital Geelong	Geelong
Australia	Calvary Mater Newcastle Hospital	New South Wales
Australia	Wollongong Hospital	Wollongong
Australia	Princess Alexandra Hospital	Woolloongabba
Belgium	Institut Jules Bordet	Anderlecht
Belgium	Ghent University Hospital	Gent
Belgium	Jolimont	Haine Saint Paul La Louviere
Belgium	Az Groeninge	Kortrijk
Belgium	Universitair Ziekenhuis Leuven	Leuven
Belgium	GZA Ziekenhuizen- Campus St Augustinus	Wilrijk
Brazil	Liga Norte Riograndense Contra O Cancer	Natal
Brazil	Hospital Sao Rafael	Salvador
Brazil	Clinica Medica Sao Germano S/S LTDA	Sao Paulo
Brazil	Hospital Das Clinicas Da Faculdade De Medicina Da USP	Sao Paulo
Canada	Tom Baker Cancer Center University of Calgary	Calgary	Alberta
China	Fujian Meidical University Union Hospital	Fu Zhou
China	Sun Yat -Sen University Cancer Center	Guangzhou
China	Renji Hospital, Shanghai Jiaotong University School of Medicine	Shanghai
China	Shanghai Fourth People s Hospital	Shanghai
China	Institute of Hematology and Blood Diseases Hospital	Tian Jin
China	Wuhan Tongji Hospital Tongji Medical College	WuHan
Czechia	Fakultni nemocnice Brno	Brno - Bohunice
Czechia	Fakultni nemocnice Hradec Kralove	Hradec Kralove
Czechia	Fakultni nemocnice Olomouc	Olomouc
Czechia	Fakultni nemocnice Ostrava	Ostrava
Czechia	Fakultni nemocnice Plzen	Plzen
Czechia	VFN v Praze	Praha
France	APHP - Hopital Henri Mondor	Creteil
France	Hopital Claude Huriez	Lille
France	CHU Nantes	Nantes
France	CHU Hopital Saint Antoine	PARIS cedex 12
France	CHU de Bordeaux - Hospital Haut-Leveque	Pessac cedex
France	CHU Lyon Sud	Pierre-Benite
France	CHU Poitiers - Hopital la Miletrie	Poitiers
France	CHU de Rennes - Hopital Pontchaillou	Rennes
France	Institut Universitaire du Cancer Toulouse Oncopole	Toulouse
Germany	Helios Kliniken Berlin Buch Gmbh	Berlin
Germany	Klinikum Nuernberg Nord	Nuernberg
Germany	Universitaetsklinikum Tuebingen der Eberhard-Karls-Universitaet, Abteilung fuer Innere Medizin II,	Tübingen
Germany	Universitaetsklinikum Wuerzburg	Würzburg
Greece	Alexandra General Hospital of Athens	Athens Attica
Greece	Anticancer Hospital of Thessaloniki Theageneio	Thessaloniki
Greece	G Papanikolaou Hospital of Thessaloniki	Thessalonikis
Israel	Rambam Medical Center	Haifa
Israel	Rabin	Petah Tikva
Israel	Sheba Medical Center	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv Yafo
Italy	A O U Sant Orsola Malpighi	Bologna
Italy	Ospedale San Raffaele	Milan
Italy	IRCCS Policlinico San Matteo, Università degli studi di Pavi	Pavia
Italy	Universita Degli Studi di Roma Tor Vergata	Roma
Italy	Istituto Clinico Humanitas	Rozzano
Italy	Azienda Ospedaliera Universitaria Citta della Salute e della Scienza di Torino	Torino
Japan	Kansai Medical University Hospital	Hirakata
Japan	Kanazawa University Hospital	Kanazawa
Japan	Yamagata University Hospital	Yamagata
Japan	Yamanashi Prefectural Central Hospital	Yamanashi
Korea, Republic of	Dong-A University Hospital	Busan
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	National Cancer Center	Goyang si
Korea, Republic of	Chonnam National University Hwasun Hospital	Hwasun
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Asan Medical Center	Seoul
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	VUMC Amsterdam	Amsterdam
Netherlands	Gelre Ziekenhuis	Apeldoorn
Netherlands	St. Antonius Ziekenhuis Nieuwegein	Nieuwegein
Netherlands	Zuyderland Medical Center	Sittard-Geleen
Norway	Oslo University Hospital HF Ulleval sykehus	Oslo
Norway	St. Olavs Hospital	Trondheim
Poland	Pratia Onkologia Katowice	Katowice
Poland	Swietokrzyskie Centrum Onkologii SPZOZ w Kielcach	Kielce
Portugal	Ccab - Hosp. de Braga	Braga
Portugal	Champalimaud Foundation Champalimaud Centre	Lisbon
Portugal	Uls Hosp. Sao Joao	Porto
Spain	Hosp. Univ. Germans Trias I Pujol	Badalona
Spain	Hosp. de La Santa Creu I Sant Pau	Barcelona
Spain	Hosp. Univ. Virgen de Las Nieves	Granada
Spain	Hosp. de Jerez de La Frontera	Jerez de la Frontera
Spain	Hosp. Univ. 12 de Octubre	Madrid
Spain	Hosp. Univ. Hm Sanchinarro	Madrid
Spain	Hosp. Univ. La Paz	Madrid
Spain	Hosp. Univ. Son Espases	Palma de Mallorca
Spain	Hosp Clinico Univ de Salamanca	Salamanca
Spain	Hosp. Mutua Terrassa	Terrassa
Spain	Hosp. Clinico Univ. de Valencia	Valencia
Sweden	Falu Lasarett	Falun
Sweden	Skanes universitetssjukhus	Lund
Sweden	Universitetssjukhuset Orebro	Örebro
Sweden	Karolinska University Hospital, Huddinge	Stockholm
Switzerland	INSELSPITAL Universitatsspital Bern	Bern
Switzerland	Kantonsspital St Gallen	St. Gallen
Turkey	Ankara University Medical Faculty	Ankara
Turkey	Liv Hospital Ankara	Ankara
Turkey	Dokuz Eylul University Medical Faculty	Izmir
Turkey	Ondokuz Mayis University	Samsun
United Kingdom	Blackpool Victoria Hospital	Blackpool
United Kingdom	Kent and Canterbury Hospital	Canterbury
United Kingdom	Western General Hospital	Edinburgh
United Kingdom	Imperial College Healthcare	London

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

Australia,  Belgium,  Brazil,  Canada,  China,  Czechia,  France,  Germany,  Greece,  Israel,  Italy,  Japan,  Korea, Republic of,  Netherlands,  Norway,  Poland,  Portugal,  Spain,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 09 years)
Primary	12-Month Minimal Residual Disease (MRD)-Negative Complete Response (CR)	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.	At Month 12
Secondary	Very Good Partial Response (VGPR) or Better	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.	From randomization up to 09 years
Secondary	Complete Response (CR) or Better	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.	From randomization up to 09 years
Secondary	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 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 09 years
Secondary	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 09 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 that starts after the next line of subsequent therapy, or death from any cause, whichever occurs first.	From randomization up to 09 years
Secondary	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 09 years)
Secondary	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 09 years
Secondary	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 09 years
Secondary	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 09 years
Secondary	Number of Participants with Abnormalities in Physical Examination	Number of participants with abnormalities in physical examination will be reported.	From randomization up to 09 years
Secondary	Number of Participants with Abnormalities in Electrocardiogram (ECG)	Number of participants with abnormalities in ECG will be reported.	From randomization up to 09 years
Secondary	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 09 years
Secondary	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 09 years
Secondary	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
Secondary	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)
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 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
Secondary	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 09 years