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)

• ClinicalTrials.gov Identifier: NCT05552222
• Recruitment Status: Recruiting
• First Posted: September 23, 2022
• Last Update Posted: April 24, 2024
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: September 21, 2022
• First Posted Date: September 23, 2022
• Last Update Posted Date: April 24, 2024
• Actual Study Start Date: October 25, 2022
• Estimated Primary Completion Date: April 30, 2031 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 21, 2023)

• Progression Free Survival (PFS) [ Time Frame: From randomization to the date of disease progression or death (Up to 9 years) ]
  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.
• Complete Response (CR) or Better [ Time Frame: From randomization up to 9 years ]
  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.

Original Primary Outcome Measures (submitted: September 21, 2022)

• Progression Free Survival (PFS) [ Time Frame: From randomization to the date of disease progression or death (Up to 7 years) ]
  PFS is defined as the duration from the date of randomization to either progressive disease or death, whichever comes first.
• Sustained Minimal Residual disease (MRD)-negative Complete Response (CR) [ Time Frame: Up to 7 years ]
  Sustained MRD-negative CR is defined as participants 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.

Current Secondary Outcome Measures (submitted: November 21, 2023)

• Very Good Partial Response (VGPR) or Better [ Time Frame: From randomization up to 9 years ]
  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.
• Sustained Minimal Residual disease (MRD)-negative Complete Response (CR) [ Time Frame: From randomization up to 9 years ]
  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.
• MRD-negative CR [ Time Frame: From randomization up to 9 years ]
  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.
• Progression Free Survival on Next-line Therapy (PFS2) [ Time Frame: From randomization up to 9 years ]
  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.
• Overall Survival (OS) [ Time Frame: From randomization to the date of death (up to 9 years) ]
  OS is defined as the time from the date of randomization to the date of death due to any cause.
• Number of Participants with Adverse Events (AEs) by Severity [ Time Frame: From randomization up to 9 years ]
  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 [ Time Frame: From randomization up to 9 years ]
  Number of participants with abnormalities in laboratory parameters (serum chemistry and hematology) will be reported.
• Number of Participants with Abnormalities in Vital Signs [ Time Frame: From randomization up to 9 years ]
  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 [ Time Frame: From randomization up to 9 years ]
  Number of participants with abnormalities in physical examination will be reported.
• Number of Participants with Abnormalities in Electrocardiogram (ECG) [ Time Frame: From randomization up to 9 years ]
  Number of participants with abnormalities in ECG will be reported.
• Serum Concentrations of Teclistamab and Talquetamab [ Time Frame: From randomization up to 9 years ]
  Serum samples will be analyzed to determine concentrations of teclistamab and talquetamab using validated, specific, and sensitive methods.
• Number of Participants with Anti-drug Antibodies (ADAs) to Teclistamab and Talquetamab [ Time Frame: From randomization up to 9 years ]
  Number of participants with ADAs to teclistamab and talquetamab will be reported.
• 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) [ Time Frame: From baseline up to 9 years ]
  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.
• Change from Baseline in Treatment-related Symptoms as Assessed by Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) [ Time Frame: Baseline through Cycle 6 (each cycle of 28 days) (up to 196 days) ]
  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.
• Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by EuroQol Five Dimension Questionnaire 5-Level (EQ-5D-5L) [ Time Frame: From baseline up to 9 years ]
  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 [ Time Frame: From randomization up to 9 years ]
  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.

Original Secondary Outcome Measures (submitted: September 21, 2022)

• Very Good Partial Response (VGPR) or Better [ Time Frame: Up to 9 years ]
  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.
• Complete Response (CR) or Better [ Time Frame: Up to 9 years ]
  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.
• MRD-negative CR [ Time Frame: Up to 9 years ]
  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.
• Progression Free Survival on Next-line Therapy (PFS2) [ Time Frame: Up to 9 years ]
  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.
• Overall Survival (OS) [ Time Frame: Up to 9 years ]
  OS is defined as the time from the date of randomization to the date of death due to any cause.
• Number of Participants with Adverse Events (AEs) by Severity [ Time Frame: Up to 9 years ]
  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 [ Time Frame: Up to 9 years ]
  Number of participants with abnormalities in laboratory parameters (serum chemistry and hematology) will be reported.
• Number of Participants with Abnormalities in Vital Signs [ Time Frame: Up to 9 years ]
  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 [ Time Frame: Up to 9 years ]
  Number of participants with abnormalities in physical examination will be reported.
• Number of Participants with Abnormalities in Electrocardiogram (ECG) [ Time Frame: Up to 9 years ]
  Number of participants with abnormalities in ECG will be reported.
• Serum Concentrations of Teclistamab [ Time Frame: Up to 9 years ]
  Serum samples will be analyzed to determine concentrations of teclistamab using validated, specific, and sensitive methods.
• Number of Participants with Anti-drug Antibodies (ADAs) to Teclistamab [ Time Frame: Up to 9 years ]
  Number of participants with ADAs to teclistamab will be reported.
• 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) [ Time Frame: Baseline up to 9 years ]
  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.
• Change from Baseline in Treatment-related Symptoms as Assessed by Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) [ Time Frame: Baseline up to Day 15 of Cycle 6 ]
  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.
• Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by EuroQol Five Dimension Questionnaire 5-Level (EQ-5D-5L) [ Time Frame: Baseline up to 9 years ]
  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 [ Time Frame: Up to 9 years ]
  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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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
• Brief 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Myeloma

Intervention

• Drug: Teclistamab
  Teclistamab will be administered as SC injection.
  Other Name: JNJ-64007957
• Drug: Daratumumab
  Daratumumab will be administered as SC injection.
• Drug: Lenalidomide
  Lenalidomide will be administered orally.
• Drug: Dexamethasone
  Dexamethasone will be administered either orally or intravenously (IV).
• Drug: Talquetamab
  Talquetamab will be administered as SC injection.
  Other Name: JNJ-64407564

Study Arms

• Experimental: Teclistamab, Daratumumab SC, and Lenalidomide (Tec-DR)
  Participants will receive teclistamab as subcutaneous (SC) injection in combination with daratumumab and lenalidomide.
  Interventions:

  • Drug: Teclistamab
  • Drug: Daratumumab
  • Drug: Lenalidomide
• Experimental: Talquetamab, Daratumumab SC, and Lenalidomide (Tal-DR)
  Participants will receive talquetamab as SC injection in combination with daratumumab and lenalidomide.
  Interventions:

  • Drug: Daratumumab
  • Drug: Lenalidomide
  • Drug: Talquetamab
• Active Comparator: Daratumumab SC, Lenalidomide, and Dexamethasone (DRd)
  Participants will receive daratumumab as SC injection with lenalidomide and dexamethasone.
  Interventions:

  • Drug: Daratumumab
  • Drug: Lenalidomide
  • Drug: Dexamethasone

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: July 14, 2023): 1590
• Original Estimated Enrollment (submitted: September 21, 2022): 1030
• Estimated Study Completion Date: October 28, 2033
• Estimated Primary Completion Date: April 30, 2031 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Study Contact; 844-434-4210; Participate-In-This-Study@its.jnj.com

• Listed Location Countries: Australia, Belgium, Czechia, France, Germany, Italy, Korea, Republic of, Netherlands, Poland, Spain, Sweden, Switzerland, Turkey, United Kingdom
• Removed Location Countries: Austria, Brazil, Canada, China, Denmark, Finland, Greece, Hungary, India, Japan, Norway, Portugal, United States

Administrative Information

• NCT Number: NCT05552222
• 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 )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• 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
• URL: https://www.janssen.com/clinical-trials/transparency

• Current Responsible Party: Janssen Research & Development, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Janssen Research & Development, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: Janssen Research & Development, LLC
• Verification Date: April 2024