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.

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

Relapsed or Refractory Multiple Myeloma

Relapsed/ Refractory Multiple Myeloma

Relapsed/Refractory Multiple Myeloma

Relapse Multiple Myeloma

Refractory Multiple Myeloma

Relapsed/Refractory Multiple Myeloma (RRMM)

Multiple Myeloma

Kahler's Disease

Blood Cancer

Hematologic Neoplasms

Hematologic Malignancies

Hematology

Hematological Malignancies

Bortezomib

Dexamethasone

Carfilzomib

Teclistamab

Pomalidomide

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

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) 2016 response criteria, or death due to any cause, whichever occurs first.

Severity for CRS will be graded as follows: Grade 1: Fever (Temperature greater than or equal to [>=] 38°C); Grade 2: Fever (Temperature >=38°C) with either: hypotension and/or hypoxia requiring low-flow nasal cannula or blow-by; Grade 3: Fever (Temperature >=38°C) with either: hypotension and/or hypoxia requiring high-flow nasal cannula, facemask, nonrebreather mask, or Venturi mask; Grade 4: Fever (Temperature >=38°C) with either: hypotension requiring multiple vasopressors (excluding vasopressin), and/or hypoxia requiring positive pressure and Grade 5: Death.

Overall response (PR or better) is defined as participants who have a PR or better prior to subsequent antimyeloma therapy in accordance with the IMWG 2016 criteria.

VGPR or better (Stringent Complete Response [sCR]+Complete Response [CR]+VGPR) is defined as participants who achieve a VGPR or better response prior to subsequent antimyeloma therapy in accordance with the IMWG 2016 criteria.

CR or better response is defined as participants who achieve a CR or better response prior to subsequent antimyeloma therapy in accordance with the IMWG 2016 criteria.

DOR is defined as the time interval between 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 2016 response criteria or death due to any cause, whichever occurs first.

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

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.

OS is defined as the time from the date of randomization to the date of the participant's death due to any cause.

Number of participants with AEs by Severity will be reported.

Number of participants with SAEs by Severity will be reported.

Number of participants with abnormal laboratory results (such as hematology and chemistry) will be reported.

Serum concentrations of teclistamab will be reported.

Number of participants with ADAs to teclistamab will be reported.

Change from baseline in symptoms, functioning, and overall HRQoL assessed by EORTC QLQ-C30 score version 3 will be reported. 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 6 single symptom items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). 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 assessed by MySIm-Q will be reported. 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 assessed by PRO-CTCAE will be reported. The National Cancer Institute's (NCI's) PRO-CTCAE is an item library of common adverse events 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 assessed by EQ-5D-5L will be reported. The EQ-5D-5L is a generic measure of health status. 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 worsening in symptoms, functioning, and overall HRQoL will be measured as the interval from the date of randomization to the start date of meaningful change.

PFS in participants in high-risk molecular features will be reported. PFS is defined as the time from the date of randomization to the date of first documented disease progression, as defined in the IMWG 2016 response criteria, or death due to any cause, whichever occurs first.

Depth of response in participants in high-risk molecular features will be reported.

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

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

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

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.

MemorialCare Long Beach Medical Center

University of California, Irvine

PIH Health Hospital

Cleveland Clinic Florida

Tulane University Hospital & Clinics

Saint Luke's Hospital - Saint Luke's Cancer Specialists

St. Vincent's Hospital Melbourne

Box Hill Hospital

Fiona Stanley Hospital

Sir Charles Gairdner Hospital

Algemeen Ziekenhuis Klina

Jolimont

Az Groeninge

Universitair Ziekenhuis Gasthuisberg

Hospitais Integradaos da Gavea S/A - DF Star

Instituto Joinvilense de Hematologia e Oncologia Ltda-Centro de Hematologia e Oncologia

Liga Norte Riograndense Contra O Cancer

Complexo Hospitalar de Niterói

Instituto de Educacao, Pesquisa e Gestao em Saude Instituto Americas (COI)

Hospital Sao Rafael

Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto - Hospital de Base

Sociedade Beneficente de Senhoras - Hospital Sírio Libanês

Fundacao Antonio Prudente - A.C. Camargo Cancer Center

Instituto D'Or de Pesquisa e Ensino (IDOR)

Real e Benemérita Associação Portuguesa de Beneficência

Hospital Alemao Oswaldo Cruz

Clinica Sao Germano

Lakeridge Health Oshawa

Beijing Chaoyang Hospital

The First Bethune Hospital of Jilin University

The Third Xiangya Hospital, Central South University

Sichuan Provincial People's Hospital

Chongqing University Cancer Hospital

Fujian Meidical University Union Hospital

Sun Yat -Sen University Cancer Center

First affiliated Hospital of Zhejiang University

Harbin medical university cancer hospital

The First Affiliated Hospital of NanChang University

First Affiliated Hospital of Guangxi Medical University

Shengjing Hospital of China Medical University

Shenzhen 2nd People's Hospital

Institute of Hematology & Blood Diseases Hospital

The First Affiliated Hospital of Wenzhou Medical University

Wuhan Union Hospital

Wuxi People's Hospital

Fakultni nemocnice Brno

Fakultni nemocnice Ostrava

Vseobecna fakultni nemocnice v Praze

Aalborg University Hospital

Rigshospitalet

Regionshospitalet Godstrup

Vejle Sygehus

CHU Amiens - Hopital Sud

Hôpital Côte de Nacre

CHU Grenoble

Centre Hospitalier du Mans

CHU de Montpellier, Hopital Saint-Eloi

CHU Nantes

Hopital de la Pitie Salpetriere

Hôpital Necker Enfants Malades

Institut Universitaire du Cancer Toulouse Oncopole

CHU de Nancy - Hôpital de Brabois

Carl-Thiem-Klinikum Cottbus gGmbH

Universitätsklinikum Carl Gustav Carus Dresden

Universitätsmedizin Greifswald

Asklepios Klinik Altona

Universitaetsklinikum Heidelberg

Heinrich-Braun-Klinikum gGmbH

Alexandra General Hospital of Athens

Agios Andreas General Hospital of Patra

'G. Papanikolaou' Hospital of Thessaloniki

Bnai Zion Medical Center

Carmel Medical Center

Rabin Medical Center

Sheba Medical Center

Tel-Aviv Sourasky Medical Center

A.O.U Sant'Orsola-Malpighi

Fondazione IRCCS Istituto Nazionale dei Tumori

Azienda Ospedaliero Universitaria Policlinico Paolo Giaccone

Arcispedale Santa Maria Nuova - IRCCS

Campus Bio-Medico di Roma

A.O. Universitaria Senese- Ospedale Santa Maria alle Scotte

A.O.U. Citta della Salute e della Scienza di Torino - Presidio Molinette

ASUI Santa Maria della Misericordia di Udine

Ospedale di Circolo e Fondazione Macchi

Chiba Cancer Center

Ogaki Municipal Hospital

Kansai Medical University Hospital

Hitachi General Hospital

Saitama Medical University Hospital

Kameda General Hospital

Kurashiki Central Hospital

Matsuyama Red Cross Hospital

JRC Nagasaki Genbaku Hospital

Niigata University Medical & Dental Hospital

National Hospital Organization Okayama Medical Center

Osaka Metropolitan University Hospital

Hokkaido University Hospital

Juntendo University Hospital

The Cancer Institute Hospital of JFCR

Participants will receive teclistamab monotherapy.

Participants will receive either PVd or Kd based on principal investigator's choice.

Rocky Mountain Cancer Centers

University of Connecticut

University of Miami Sylvester Cancer Center

Boston University Medical Center

Saint Lukes Hospital Saint Lukes Cancer Specialists

CHR de la Citadelle

Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto Hospital de Base

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

Trials at a glance

Trials at a glance

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

Outcome measures

Primary outcome measures

Secondary outcome measures