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A Phase 3 Randomized Study Comparing Teclistamab in Combination with Daratumumab 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 (MajesTEC-3)

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 (MajesTEC-3)

Nishikawa Kazuk

Janssen Pharmaceutical K.K.

3-5-2 Nishikanda Chiyoda-ku Tokyo

DL-JANJP-JCO_TL_TSG_EMP@its.jnj.com

Medical Information Center

Janssen Pharmaceutical K.K.

3-5-2 Nishikanda Chiyoda-ku Tokyo

+81-120-183-275

DL-JANJP-JCO_TL_TSG_EMP@its.jnj.com

Recruiting

May. 27, 2022

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

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:
a. 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, b. 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, Waldenstrom's macroglobulinemia, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes), or primary amyloid light chain amyloidosis

Both

Multiple Myeloma

Daratumumab
Arm A: Teclistamab-daratumumab (Tec-Dara)
Arm B:Daratumumab,Pomalidomide,Dexamethasone (DPd) or Daratumumab, Bortezomib,Dexamethasone (DVd)
Daratumumab will be administered SC injection.

Pomalidomide
Arm B:DPd or DVd
Pomalidomide will be administered orally.

Dexamethasone
Arm B:DPd or DVd
Dexamethasone will be administered orally or intravenously.

Bortezomib
Arm B:DPd or DVd
Bortezomib will be administered SC injection.

Teclistamab
Arm A: Teclistamab-daratumumab (Tec-Dara)
Teclistamab will be administered SC injection.

Progression Free Survival (PFS)
Up to 5 years
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.

Overall Response (Partial Response [PR] or Better)
Up to 5 years
Overall response (PR or better) is defined as participants who have a PR or better per IMWG criteria.

Very Good Partial Response (VGPR) or Better
Up to 5 years
VGPR or better is defined as participants who achieve a VGPR or better response per IMWG criteria.

Complete Response (CR) or Better
Up to 5 years
CR or better is defined as participants who achieve a CR or better response per IMWG criteria.

Minimal Residual Disease (MRD)-negativity
Up to 5 years
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.

Progression Free Survival on Next-line Therapy (PFS2)
Up to 5 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 on the first subsequent line of antimyeloma therapy, or death from any cause, whichever occurs first.

Overall Survival (OS)
Up to 5 years
OS is measured from the date of randomization to the date of the participants death.

Time to Next Treatment (TTNT)
Up to 5 years
TTNT is defined as the interval time from randomization to the start of subsequent antimyeloma treatment.

Duration of Response
Up to 5 years
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.

Number of Participants with Adverse Events (AEs) by Severity
Up to 5 years
Number of participants with AEs by Severity will be reported.

Serum Concentration of Teclistamab
Up to 5 years
Serum samples will be analyzed to determine concentrations of teclistamab using a validated, specific, and sensitive method.

Number of Participants with Anti-drug Antibodies (ADAs) to Teclistamab and Daratumumab
Up to 5 years
Number of participants with ADAs to teclistamab and daratumumab will be reported.

Time to Worsening of Symptoms
Up to 5 years
Time to worsening is measured as the interval from the date of randomization to the start date of meaningful change.

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)
Baseline Up to 5 years
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.

Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by Multiple Myeloma Symptom and Impact Questionnaire (MySIm-Q) Scale Score
Baseline Up to 5 years
The MySIm-Q is a disease-specific PRO assessment complementary to the EORTC-QLQ-C30. It includes 17 items resulting in a symptom subscale and an impact subscale. The recall period is the past 7 days, and responses are reported on a 5-point verbal rating scale.

Change from Baseline in Symptoms, Functioning, and Overall HRQoL as Assessed by Patient-reported Outcomes Measurement Information System Short Form v2.0-Physical Function 8c (PROMIS PF 8c)
Baseline Up to 5 years
The PROMIS-SD is used to assess self-reported perceptions of sleep quality, sleep depth and restoration associated with sleep. The 8-item short form will be used in this study, in which responses are scored 1 to 5 for each item. Higher overall score indicates more sleep disturbance.

Others: See attached file.

+81-96-373-5842

Mar. 16, 2022

Yes

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale open Data Access (YODA) Project site at yoda.yale.edu

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