Multiple Myeloma
Conditions
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).
Interventions
DRUGTeclistamab
Teclistamab will be administered as SC injection.
DRUGDaratumumab
Daratumumab will be administered as SC injection.
DRUGLenalidomide
Lenalidomide will be administered orally.
DRUGDexamethasone
Dexamethasone will be administered either orally or intravenously (IV).
DRUGTalquetamab
Talquetamab will be administered as SC injection.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | From randomization to the date of disease progression or death (Up to 09 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. |
| 12-Month Minimal Residual Disease (MRD)-Negative Complete Response (CR) | At Month 12 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | From randomization to the date of death (up to 09 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 | From randomization up to 09 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 | From randomization up to 09 years | Number of participants with abnormalities in laboratory parameters (serum chemistry and hematology) will be reported. |
| Number of Participants with Abnormalities in Vital Signs | From randomization up to 09 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 | From randomization up to 09 years | Number of participants with abnormalities in physical examination will be reported. |
| Number of Participants with Abnormalities in Electrocardiogram (ECG) | From randomization up to 09 years | Number of participants with abnormalities in ECG will be reported. |
| Serum Concentrations of Teclistamab and Talquetamab | From randomization up to 09 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 | From randomization up to 09 years | Number of participants with ADAs to teclistamab and talquetamab will be reported. |
| Sustained Minimal Residual disease (MRD)-negative Complete Response (CR) | From randomization up to 09 years | 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. |
| Very Good Partial Response (VGPR) or Better | From randomization up to 09 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 IMWG criteria during or after the study treatment. |
| Complete Response (CR) or Better | From randomization up to 09 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. |
| 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) | 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) | 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) | 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). |
| MRD-negative CR | From randomization up to 09 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. |
| Time to Sustained Worsening in Symptoms, Functioning, and HRQoL | From randomization up to 09 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. |
| Progression Free Survival on Next-line Therapy (PFS2) | From randomization up to 09 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. |
Countries
Australia, Austria, Belgium, Brazil, Canada, China, Czechia, Denmark, France, Germany, Greece, Israel, Italy, Japan, Netherlands, Norway, Poland, Portugal, South Korea, Spain, Sweden, Switzerland, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTStudy Contact
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Outcome results
None listed