A Study Comparing Teclistamab Monotherapy Versus Pomalidomide, Bortezomib, Dexamethasone (PVd) or Carfilzomib, Dexamethasone (Kd) in Participants With Relapsed or Refractory Multiple Myeloma (MajesTEC-9)

Janssen (J&J Innovative Medicine)

Status and phase: Enrolling; Phase 3

Conditions: Relapsed or Refractory Multiple Myeloma

Treatments: Drug: Dexamethasone; Drug: Pomalidomide; Drug: Teclistamab; Drug: Carfilzomib; Drug: Bortezomib

Study type: Interventional

Funder types: Industry

Identifiers

NCT05572515

2023-503444-13-00 (Registry Identifier)

64007957MMY3006 (Other Identifier)

CR109244

2022-000928-37 (EudraCT Number)

Details and patient eligibility

About

The purpose of this study is to compare the efficacy of teclistamab with PVd/Kd in Part 1 and to further characterize safety and efficacy of an alternative dosing for teclistamab in Part 2 in participants with relapsed or refractory multiple myeloma.

Enrollment: 650 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Documented diagnosis of multiple myeloma as defined by the criteria below: (a)Multiple myeloma diagnosis according to 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 grams per deciliter (g/dL) (central laboratory); or (2) Urine M-protein level >=200 milligrams (mg)/24 hours (central laboratory); or (3) Serum immunoglobulin free light chain >=10 milligrams per deciliter (mg/dL) (central laboratory) and abnormal serum immunoglobulin kappa lambda free light chain ratio
• Received 1 to 3 prior lines of antimyeloma therapy including a minimum of 2 consecutive cycles of an anti- cluster of differentiation 38 (CD38) monoclonal antibody at the approved dosing regimen in any prior line and 2 consecutive cycles of lenalidomide in any prior line
• Documented evidence of progressive disease or failure to achieve a response to last line of therapy based on investigator's determination of response by International myeloma working group (IMWG) criteria
• Have an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2
• A female participant must agree not to be pregnant, breast-feeding, or plan to become pregnant while enrolled in this study or within 6 months after the last dose of study treatment
• Must be willing and able to adhere to the lifestyle restrictions specified in this protocol

Exclusion criteria

• Received any prior B cell maturation antigen (BCMA)-directed therapy
• A participant is not eligible to receive PVd as control therapy if any of the following are present: (1) Received prior pomalidomide therapy, (2) Does not meet criteria for bortezomib retreatment (3) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to pomalidomide or bortezomib, (4) Grade 1 peripheral neuropathy with pain or Grade greater than or equal to (>=) 2 peripheral neuropathy as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0, (5) Received a strong cytochrome P (CYP) 3A4 inducer within 5 half-lives prior to randomization; A participant is not eligible to receive Kd as control therapy if any of the following are present:(1) Received prior carfilzomib therapy, (2) Uncontrolled hypertension, defined as an average systolic blood pressure greater than (>)159 millimeters of mercury (mmHg) or diastolic blood pressure >99 mmHg despite optimal treatment (3) Grade 2 peripheral neuropathy with pain or Grade >=3 peripheral neuropathy as defined by NCI-CTCAE Version 5.0, (4) Contraindications or life-threatening allergies, hypersensitivity, or intolerance to carfilzomib (intolerance defined as prior therapy discontinued due to any adverse event [AE] related to carfilzomib)
• Received a maximum cumulative dose of corticosteroids of >=140 mg of prednisone or equivalent within 14 days prior to randomization
• Received a live, attenuated vaccine within 4 weeks before randomization
• Central nervous system (CNS) involvement or clinical signs of meningeal involvement of multiple myeloma
• Plasma cell leukemia at the time of screening, Waldenstrom's macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, M-protein (POEMS) syndrome and skin changes, or primary amyloid light chain amyloidosis

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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650 participants in 2 patient groups

Teclistamab

Experimental group

Description:

Participants will receive teclistamab monotherapy in Part 1 and an alternative dosing regimen of teclistamab in Part 2.

Treatment:

Drug: Teclistamab

Pomalidomide, Bortezomib and Dexamethasone (PVd) or Carfilzomib and Dexamethasone (Kd)

Experimental group

Description:

Participants will receive either PVd or Kd based on principal investigator's choice during Part 1 of the study.

Treatment:

Drug: Bortezomib

Drug: Carfilzomib

Drug: Pomalidomide

Drug: Dexamethasone