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
Trial Snapshot
- Phase
- Phase 3
- Status
- Recruiting
- Enrollment
- 1,590
- Locations
- 299
- Primary Endpoint
- Progression Free Survival (PFS)
Study Overview
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).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts 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
Arms & Interventions
Teclistamab, Daratumumab SC, and Lenalidomide (Tec-DR)
Participants will receive teclistamab as subcutaneous (SC) injection in combination with daratumumab and lenalidomide.
Intervention: Lenalidomide (Drug)
Daratumumab SC, Lenalidomide, and Dexamethasone (DRd)
Participants will receive daratumumab as SC injection with lenalidomide and dexamethasone.
Intervention: Lenalidomide (Drug)
Daratumumab SC, Lenalidomide, and Dexamethasone (DRd)
Participants will receive daratumumab as SC injection with lenalidomide and dexamethasone.
Intervention: Dexamethasone (Drug)
Talquetamab, Daratumumab SC, and Lenalidomide (Tal-DR)
Participants will receive talquetamab as SC injection in combination with daratumumab and lenalidomide.
Intervention: Talquetamab (Drug)
Daratumumab SC, Lenalidomide, and Dexamethasone (DRd)
Participants will receive daratumumab as SC injection with lenalidomide and dexamethasone.
Intervention: Daratumumab (Drug)
Talquetamab, Daratumumab SC, and Lenalidomide (Tal-DR)
Participants will receive talquetamab as SC injection in combination with daratumumab and lenalidomide.
Intervention: Daratumumab (Drug)
Talquetamab, Daratumumab SC, and Lenalidomide (Tal-DR)
Participants will receive talquetamab as SC injection in combination with daratumumab and lenalidomide.
Intervention: Lenalidomide (Drug)
Teclistamab, Daratumumab SC, and Lenalidomide (Tec-DR)
Participants will receive teclistamab as subcutaneous (SC) injection in combination with daratumumab and lenalidomide.
Intervention: Daratumumab (Drug)
Teclistamab, Daratumumab SC, and Lenalidomide (Tec-DR)
Participants will receive teclistamab as subcutaneous (SC) injection in combination with daratumumab and lenalidomide.
Intervention: Teclistamab (Drug)
Outcomes
Primary Outcomes
Progression Free Survival (PFS)
Time Frame: 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)
Time Frame: 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 Outcomes
- Number of Participants with Abnormalities in Vital Signs(From randomization up to 09 years)
- Sustained Minimal Residual disease (MRD)-negative Complete Response (CR)(From randomization up to 09 years)
- Number of Participants with Abnormalities in Physical Examination(From randomization up to 09 years)
- Serum Concentrations of Teclistamab and Talquetamab(From randomization up to 09 years)
- Number of Participants with Anti-drug Antibodies (ADAs) to Teclistamab and Talquetamab(From randomization up to 09 years)
- MRD-negative CR(From randomization up to 09 years)
- Progression Free Survival on Next-line Therapy (PFS2)(From randomization up to 09 years)
- Overall Survival (OS)(From randomization to the date of death (up to 09 years))
- Number of Participants with Adverse Events (AEs) by Severity(From randomization up to 09 years)
- Number of Participants with Abnormalities in Laboratory Parameters(From randomization up to 09 years)
- Very Good Partial Response (VGPR) or Better(From randomization up to 09 years)
- Complete Response (CR) or Better(From randomization up to 09 years)
- Time to Sustained Worsening in Symptoms, Functioning, and HRQoL(From randomization up to 09 years)
- 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)
- Number of Participants with Abnormalities in Electrocardiogram (ECG)(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)(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)(Baseline through Cycle 6 (each cycle of 28 days) (up to 196 days))