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).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
1,590
Teclistamab will be administered as SC injection.
Daratumumab will be administered as SC injection.
Lenalidomide will be administered orally.
Dexamethasone will be administered either orally or intravenously (IV).
Talquetamab will be administered as SC injection.
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States
RECRUITINGUniversity of Arizona Cancer Center
Tucson, Arizona, United States
RECRUITINGUCSF Fresno
Clovis, California, United States
RECRUITINGCity of Hope Duarte
Duarte, California, United States
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.
Time frame: From randomization to the date of disease progression or death (Up to 09 years)
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.
Time frame: At Month 12
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.
Time frame: From randomization up to 09 years
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.
Time frame: From randomization up to 09 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 NGS with sensitivity of 10\^-5, for at least 12 months without any examination showing MRD positive status or progressive disease in between.
Time frame: From randomization up to 09 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.
Time frame: From randomization up to 09 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.
Time frame: From randomization up to 09 years
Overall Survival (OS)
OS is defined as the time from the date of randomization to the date of death due to any cause.
Time frame: From randomization to the date of death (up to 09 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.
Time frame: From randomization up to 09 years
Number of Participants with Abnormalities in Laboratory Parameters
Number of participants with abnormalities in laboratory parameters (serum chemistry and hematology) will be reported.
Time frame: From randomization up to 09 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.
Time frame: From randomization up to 09 years
Number of Participants with Abnormalities in Physical Examination
Number of participants with abnormalities in physical examination will be reported.
Time frame: From randomization up to 09 years
Number of Participants with Abnormalities in Electrocardiogram (ECG)
Number of participants with abnormalities in ECG will be reported.
Time frame: From randomization up to 09 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.
Time frame: From randomization up to 09 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.
Time frame: From randomization up to 09 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.
Time frame: 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.
Time frame: 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).
Time frame: 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.
Time frame: From randomization up to 09 years
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City of Hope Orange County Lennar Foundation Cancer Center
Irvine, California, United States
RECRUITINGCancer and Blood Specialty Clinic
Los Alamitos, California, United States
RECRUITINGValkyrie Clinical Trials
Los Angeles, California, United States
RECRUITINGUniversity of Connecticut
Farmington, Connecticut, United States
RECRUITINGYale New Haven Hospital
New Haven, Connecticut, United States
RECRUITINGChristianaCare Helen F Graham Cancer Center and Research Institute
Newark, Delaware, United States
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