A Study of Teclistamab in Combination With Daratumumab Subcutaneously (SC) (Tec-Dara) Versus Daratumumab SC, Pomalidomide, and Dexamethasone (DPd) or Daratumumab SC, Bortezomib, and Dexamethasone (DVd) in Participants With Relapsed or Refractory Multiple Myeloma

Phase 3Active Not RecruitingNCT05083169

Janssen Research & Development, LLC587 enrolled

Overview

The purpose of this study is to compare the efficacy of teclistamab daratumumab (Tec-Dara) with daratumumab subcutaneously (SC) in combination with pomalidomide and dexamethasone (DPd) or daratumumab SC in combination with bortezomib and dexamethasone (DVd).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

587

Conditions

Multiple Myeloma

Interventions

DaratumumabDRUG

Daratumumab will be administered SC injection.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Documented multiple myeloma as defined by the criteria: a. multiple myeloma diagnosis according to the International Myeloma Working Group (IMWG) diagnostic criteria, b. measurable disease at screening as defined by any of the following: 1) serum M-protein level greater than or equal to (\>=) 0.5 gram per deciliter (g/dL); or 2) urine M-protein level \>=200 milligrams (mg)/24 hours; or 3) serum immunoglobulin free light chain \>=10 mg/dL and abnormal serum immunoglobulin kappa lambda free light chain ratio * Received 1 to 3 prior line(s) of antimyeloma therapy including a proteasome inhibitor (PI) and lenalidomide; a. participants who have received only 1 line of prior line of antimyeloma therapy must be lenalidomide refractory. Stable disease or progression on or within 60 days of the last dose of lenalidomide given as maintenance will meet this criterion * Documented evidence of progressive disease based on investigator's determination of response by IMWG criteria on or after their last regimen * Have an eastern cooperative oncology group (ECOG) performance status score of 0, 1, or 2 at screening and prior to the start of administration of study treatment * Have clinical laboratory values within the specified range Exclusion Criteria: * Contraindications or life-threatening allergies, hypersensitivity, or intolerance to any study drug or its excipients. Additional exclusion criteria pertaining to specific study drugs include: 1. A participant is not eligible to receive daratumumab subcutaneous (SC) in combination with pomalidomide and dexamethasone (DPd) as control therapy if any of the following are present: 1) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to pomalidomide, 2) Disease that is considered refractory to pomalidomide per IMWG, 2. A participant is not eligible to receive daratumumab SC in combination with bortezomib and dexamethasone (DVd) as control therapy if any of the following are present: 1) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to bortezomib, 2) Grade 1 peripheral neuropathy with pain or Grade \>= 2 peripheral neuropathy as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0, 3) Disease that is considered refractory to bortezomib per IMWG, 4) Received a strong cytochromes P450 (CYP3A4) inducer within 5 half-lives prior to randomization * Received any prior B cell maturation antigen (BCMA)-directed therapy * Has disease that is considered refractory to an anti-cluster of differentiation 38 (CD38) monoclonal antibody per IMWG * Received a cumulative dose of corticosteroids equivalent to \>=140 mg of prednisone within 14 days before randomization * Received a live, attenuated vaccine within 4 weeks before randomization * Plasma cell leukemia at the time of screening, Waldenström's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), or primary amyloid light chain amyloidosis

Locations (176)

University of Alabama Birmingham

Birmingham, Alabama, United States

City of Hope

Duarte, California, United States

Stanford University Medical Center

Stanford, California, United States

Yale University

New Haven, Connecticut, United States

Emory University Winship Cancer Institute

Atlanta, Georgia, United States

Outcomes

Primary Outcomes

Progression Free Survival (PFS)

PFS is defined as the time from the date of randomization to the date of first documented disease progression, as defined in the International Myeloma Working Group (IMWG) criteria, or death due to any cause, whichever occurs first.

Time frame: Up to 5 years

Secondary Outcomes

Overall Response (Partial Response [PR] or Better)

Overall response (PR or better) is defined as participants who have a PR or better per IMWG criteria.

Time frame: Up to 5 years

Very Good Partial Response (VGPR) or Better

VGPR or better is defined as participants who achieve a VGPR or better response per IMWG criteria.

Time frame: Up to 5 years

Complete Response (CR) or Better

CR or better is defined as participants who achieve a CR or better response per IMWG criteria.

Time frame: Up to 5 years

Minimal Residual Disease (MRD)-negativity

MRD-negativity is defined as participants who achieve MRD negativity at a threshold of 10\^-5 at any timepoint after the date of randomization and before disease progression or start of subsequent antimyeloma therapy.

Time frame: Up to 5 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 on the first subsequent line of antimyeloma therapy, or death from any cause, whichever occurs first.

Time frame: Up to 5 years

Overall Survival (OS)

OS is measured from the date of randomization to the date of the participant's death.

Time frame: Up to 5 years

Time to Next Treatment (TTNT)

TTNT is defined as the interval time from randomization to the start of subsequent antimyeloma treatment.

Time frame: Up to 5 years

Duration of Response

Duration of response will be calculated among responders (with a PR or better response) from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease according to the IMWG response criteria, or death due to any cause, whichever occurs first.

Time frame: Up to 5 years

Number of Participants with Adverse Events (AEs) by Severity

Number of participants with AEs by Severity will be reported.

Time frame: Up to 5 years

Serum Concentration of Teclistamab

Serum samples will be analyzed to determine concentrations of teclistamab using a validated, specific, and sensitive method.

Time frame: Up to 5 years

Number of Participants with Anti-drug Antibodies (ADAs) to Teclistamab and Daratumumab

Number of participants with ADAs to teclistamab and daratumumab will be reported.

Time frame: Up to 5 years

Time to Worsening of Symptoms

Time to worsening is measured as the interval from the date of randomization to the start date of meaningful change.

Time frame: Up to 5 years

Change from Baseline in Symptoms, Functioning, and Overall 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 in 5 functional scales (physical, role, emotional, cognitive, and social), 1 global health status scale, 3 symptom scales (pain, fatigue, and nausea/vomiting), and 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The 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.