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

Phase 3

Recruiting

• Conditions: Multiple Myeloma
• Interventions: Drug: Teclistamab; Drug: Daratumumab; Drug: Lenalidomide; Drug: Talquetamab; Drug: Dexamethasone

• Registration Number: NCT05552222
• Lead Sponsor: Janssen Research & Development, LLC

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 available

Study Timeline

• Study First Submitted: 2022-09-21
• Study First Submitted QC: 2022-09-21
• Study First Posted: 2022-09-23
• Study Start: 2022-10-25
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-22
• Last Update Posted: 2025-05-23
• Primary Completion: 2031-04-30
• Study Completion: 2033-10-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1590

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Teclistamab, Daratumumab SC, and Lenalidomide (Tec-DR)	Teclistamab	Participants will receive teclistamab as subcutaneous (SC) injection in combination with daratumumab and lenalidomide.
Teclistamab, Daratumumab SC, and Lenalidomide (Tec-DR)	Daratumumab	Participants will receive teclistamab as subcutaneous (SC) injection in combination with daratumumab and lenalidomide.
Teclistamab, Daratumumab SC, and Lenalidomide (Tec-DR)	Lenalidomide	Participants will receive teclistamab as subcutaneous (SC) injection in combination with daratumumab and lenalidomide.
Talquetamab, Daratumumab SC, and Lenalidomide (Tal-DR)	Daratumumab	Participants will receive talquetamab as SC injection in combination with daratumumab and lenalidomide.
Talquetamab, Daratumumab SC, and Lenalidomide (Tal-DR)	Lenalidomide	Participants will receive talquetamab as SC injection in combination with daratumumab and lenalidomide.
Talquetamab, Daratumumab SC, and Lenalidomide (Tal-DR)	Talquetamab	Participants will receive talquetamab as SC injection in combination with daratumumab and lenalidomide.
Daratumumab SC, Lenalidomide, and Dexamethasone (DRd)	Daratumumab	Participants will receive daratumumab as SC injection with lenalidomide and dexamethasone.
Daratumumab SC, Lenalidomide, and Dexamethasone (DRd)	Lenalidomide	Participants will receive daratumumab as SC injection with lenalidomide and dexamethasone.
Daratumumab SC, Lenalidomide, and Dexamethasone (DRd)	Dexamethasone	Participants will receive daratumumab as SC injection with lenalidomide and dexamethasone.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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.
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.
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.
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.
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).
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.
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.
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.
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.

Trial Locations

Locations (207)

City of Hope Cancer Center; 🇺🇸 Duarte, California, United States

City of Hope Orange County Lennar Foundation Cancer Center; 🇺🇸 Irvine, California, United States

Yale New Haven Hospital; 🇺🇸 New Haven, Connecticut, United States

University of Iowa Health Care; 🇺🇸 Waukee, Iowa, United States

Norton Cancer Institute; 🇺🇸 Louisville, Kentucky, United States

Cancer And Hematology Centers of Western Michigan PC; 🇺🇸 Grand Rapids, Michigan, United States

Nebraska Cancer Specialists; 🇺🇸 Omaha, Nebraska, United States

University of Nebraska Medical Center; 🇺🇸 Omaha, Nebraska, United States

Christus St. Vincent Regional Cancer Center; 🇺🇸 Santa Fe, New Mexico, United States

Durham VAMC; 🇺🇸 Durham, North Carolina, United States

Scroll for more (197 remaining)