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

Study Overview
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Brief Summary
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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).

Official Title
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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

Conditions
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Multiple Myeloma

Intervention / Treatment
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* Drug: Teclistamab
* Drug: Daratumumab
* Drug: Lenalidomide
* Drug: Dexamethasone
* Drug: Talquetamab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Teclistamab, Daratumumab SC, and Lenalidomide (Tec-DR)<br>Participants will receive teclistamab as subcutaneous (SC) injection in combination with daratumumab and lenalidomide. | Drug: Teclistamab<br>* Teclistamab will be administered as SC injection.<br>* Other names: JNJ-64007957;Drug: Daratumumab<br>* Daratumumab will be administered as SC injection.<br>Drug: Lenalidomide<br>* Lenalidomide will be administered orally.<br>|
| Experimental: Talquetamab, Daratumumab SC, and Lenalidomide (Tal-DR)<br>Participants will receive talquetamab as SC injection in combination with daratumumab and lenalidomide. | Drug: Daratumumab<br>* Daratumumab will be administered as SC injection.<br>Drug: Lenalidomide<br>* Lenalidomide will be administered orally.<br>Drug: Talquetamab<br>* Talquetamab will be administered as SC injection.<br>* Other names: JNJ-64407564;|
| Active Comparator: Daratumumab SC, Lenalidomide, and Dexamethasone (DRd)<br>Participants will receive daratumumab as SC injection with lenalidomide and dexamethasone. | Drug: Daratumumab<br>* Daratumumab will be administered as SC injection.<br>Drug: Lenalidomide<br>* Lenalidomide will be administered orally.<br>Drug: Dexamethasone<br>* Dexamethasone will be administered either orally or intravenously (IV).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 9 years) | 
| Complete Response (CR) or Better | 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. | From randomization up to 9 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Very Good Partial Response (VGPR) or Better | 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. | From randomization up to 9 years | 
| 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 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. | From randomization up to 9 years | 
| 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 9 years | 
| 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 9 years | 
| 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 9 years) | 
| 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 9 years | 
| 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 9 years | 
| 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 9 years | 
| Number of Participants with Abnormalities in Physical Examination | Number of participants with abnormalities in physical examination will be reported. | From randomization up to 9 years | 
| Number of Participants with Abnormalities in Electrocardiogram (ECG) | Number of participants with abnormalities in ECG will be reported. | From randomization up to 9 years | 
| 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 9 years | 
| 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 9 years | 
| 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 | 
| 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) | 
| 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 | 
| 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 9 years |