Full Title:: A Phase 3 Randomized Study Comparing Teclistamab Monotherapy Versus Pomalidomide, Bortezomib, Dexamethasone (PVd) or Carfilzomib, Dexamethasone (Kd) in Participants With Relapsed or Refractory Multiple Myeloma Who Have Received 1 to 3 Prior Lines of Therapy, Including an Anti-CD38 Monoclonal Antibody and Lenalidomide

Myeloma stage or condition:: Relapsed or Refractory Multiple Myeloma

Study phase:: Phase 3

Summary/Purpose:: The purpose of this study is to compare the efficacy of teclistamab with PVd/Kd.

Detailed Description:: Multiple myeloma is an incurable, malignant, plasma cell disorder. Teclistamab (JNJ-64007957) is a full-size, Immunoglobulin G (IgG) 4 proline, alanine, and alanine (PAA) bispecific antibody that targets the cluster of differentiation (CD3) receptor expressed on the surface of T cells and B cell maturation antigen (BCMA). With its dual binding sites, teclistamab is able to draw CD3 positive T cells in close proximity to BCMA positive cells, resulting in T-cell activation and subsequent lysis of BCMA positive cells. Pomalidomide is a third-generation immunomodulatory imide drug (IMiD) that exerts potent, direct tumoricidal and immune-enhancing effects and Carfilzomib is a second-generation proteasome inhibitor that inhibits proteasome which results in disruption of protein turnover and induces apoptosis. The primary hypothesis of this study is that teclistamab monotherapy (Arm A) will significantly improve progression free survival (PFS) compared with investigator's choice of PVd or Kd (Arm B) in participants with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide. The study will include a screening phase, treatment phase, and follow-up phase. Safety will be assessed by physical examinations, neurologic examinations, eastern cooperative oncology group (ECOG) performance status, clinical laboratory tests, vital signs, and AE monitoring. The overall duration of the study will be up to 9 years.

Treatments:: Drug : Teclistamab

Teclistamab will be administered subcutaneously.; Drug : Pomalidomide

Pomalidomide will be administered orally.; Drug : Bortezomib

Bortezomib will be administered subcutaneously.; Drug : Dexamethasone

Dexamethasone will be administered orally in PVd and intravenously or orally in Kd.; Drug : Carfilzomib

Carfilzomib will be administered intravenously.

Study Arms:: Experimental : Teclistamab
Participants will receive teclistamab monotherapy.; Experimental : Pomalidomide, Bortezomib and Dexamethasone (PVd) or Carfilzomib and Dexamethasone (Kd)
Participants will receive either PVd or Kd based on principal investigator's choice.

Study Type:: Interventional

Study Design:: Allocation: Randomized; Intervention Model: Parallel Assignment; Primary Purpose: Treatment; Masking: None (Open Label)

Recruitment status:: Recruiting

Eligibility criteria:

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)
Central nervous system (CNS) involvement or clinical signs of meningeal involvement of multiple myeloma.
Received a live, attenuated vaccine within 4 weeks before randomization
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
Received a maximum cumulative dose of corticosteroids of >=140 mg of prednisone or equivalent within 14 days prior to randomization

Locations / Centres:

Tom Baker Cancer Centre, Calgary, Alberta – Recruiting

Saint John Regional Hospital, Saint John, New Brunswick – Recruiting

Brampton Civic Hospital, Brampton, Ontario – Recruiting

Lakeridge Health Oshawa, Oshawa, Ontario – Recruiting

CIUSSS de l'Est-de-l'Île-de-Montréal Installation Hôpital Maisonneuve-Rosemont, Montreal, Quebec – Recruiting

Contacts:: Name: Study Contact
Phone: 844-434-4210
Email: [email protected]

Publications:: ???

First posted:: 2022-10-07

Actual start date:: March 29, 2023

Last updated:: 2024-04-23

Estimated enrollment:: 590

Estimated completion date:: 2031-08-31

Estimated primary completion date:: 2025-10-14

Condition:: Relapsed or Refractory Multiple Myeloma

Gender:: All

Ages:: 18 Years-N/A

Accepts healthy volunteers:: No

Listed location countries:: Australia; Austria; Belgium; Brazil; Canada; China; Czechia; Denmark; France; Germany; Greece; India; Israel; Italy; Japan; Malaysia; Netherlands; Poland; Portugal; Spain; Sweden; Turkey; United Kingdom; United States

NCT number:: NCT05572515

Other study ID numbers:: CR109244

Has Data monitoring committee:: Yes

U.S. FDA-regulated product:: Yes

IPD Sharing Statement :: ???

Responsible party:: Sponsor

Study sponsor:: lead_sponsor
Janssen Research & Development, LLC
Industry

Collaborators:: ???

Investigators:: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Protocol Registration and Results System:: ???

Verification date:: 2024-04-01

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