A Study of Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma (MajesTEC-1)

A Phase 1/2, First-in-Human, Open-Label, Dose Escalation Study of Teclistamab, a Humanized BCMA x CD3 Bispecific Antibody, in Subjects With Relapsed or Refractory Multiple Myeloma

The purpose of this study is to evaluate the efficacy of teclistamab at the recommended Phase 2 dose (RP2D).

Study Overview

• Status: Active, not recruiting
• Conditions: Hematological Malignancies
• Intervention / Treatment: Drug: Teclistamab

Detailed Description

Study record NCT03145181 is Phase 1 part of this study and study record NCT04557098 is Phase 2 part of this study.

• Study Type: Interventional
• Enrollment (Actual): 194
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Study Contact; Phone Number: 844-434-4210; Email: Participate-In-This-Study@its.jnj.com

Study Locations

• Belgium
  • Gent, Belgium, 9000
    • Universitair Ziekenhuis Gent - UZ GENT
  • Leuven, Belgium, 3000
    • Universitaire Ziekenhuizen Leuven
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Tom Baker Cancer Centre
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Cross Cancer Institute
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network (UHN) Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H4A 3J1
      • McGill University Health Centre
• China
  • Beijing, China, 100034
    • Peking University First Hospital
  • Chengdu, China, 610041
    • West China Hospital Si Chuan University
  • Guangzhou, China, 510060
    • Sun Yat -Sen University Cancer Center
  • Hangzhou, China, 310003
    • First affiliated Hospital of Zhejiang University
  • Shanghai, China, 200003
    • Shanghai Changzheng Hospital
  • Shenyang, China, 110004
    • Shengjing Hospital of China Medical University
  • Tianjin, China, 30060
    • Tianjin Medical University Cancer Institute and Hospital
  • Xi'an, China, 710004
    • The Second Affiliated Hospital of Xi'an Jiaotong University
• France
  • Lille Cedex, France, 59000
    • Centre Hospitalier Régional Universitaire de Lille, Hôpital Claude Huriez
  • Nantes, France, 44093
    • C.H.U. Hotel Dieu - France
  • Pierre Benite, France, 69495
    • Centre Hospitalier Lyon Sud
  • Poitiers, France, 86021
    • CHRU Hôpital Jean Bernard
  • Toulouse cedex 9, France, 31059
    • Pôle IUC Oncopole CHU
  • Tours, France, 37044
    • CHRU Hôpital Bretonneau
• Germany
  • Heidelberg, Germany, 69120
    • Universitaetsklinikum Heidelberg
  • Leipzig, Germany, 04103
    • Universitaetsklinikum Leipzig
  • Tübingen, Germany, 72076
    • Universitaetsklinikum Tuebingen der Eberhard-Karls-Universitaet, Abteilung fuer Innere Medizin II,
  • Wuerzburg, Germany, 97080
    • Universitätsklinikum Würzburg
• Italy
  • Bergamo, Italy, 24127
    • Azienda Ospedaliera Papa Giovanni Xxiii
  • Bologna, Italy, 40138
    • Istituto di Ematologia Seràgnoli azienda ospedaliera univeristaria Policlinico S.Orsola-Malpighi
  • Milano, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • VU Medisch Centrum
• Spain
  • Badalona, Spain, 08916
    • Hosp. Univ. Germans Trias I Pujol
  • Barcelona, Spain, 08036
    • Hosp. Clinic de Barcelona
  • Madrid, Spain, 28041
    • Hosp. Univ. 12 de Octubre
  • Pamplona, Spain, 31008
    • Clinica Univ. de Navarra
  • Pozuelo de Alarcon, Spain, 28223
    • Hosp. Quiron Madrid Pozuelo
  • Salamanca, Spain, 37007
    • Hosp. Clinico Univ. de Salamanca
  • Santander, Spain, 39008
    • Hosp. Univ. Marques de Valdecilla
• Sweden
  • Göteborg, Sweden, 413 45
    • Sahlgrenska University Hospital
  • Lund, Sweden, 221 85
    • Skane University Hospital
  • Stockholm, Sweden, SE-141 86
    • Haematology Centre, R 51
• United Kingdom
  • London, United Kingdom, NW1 2PG
    • University College Hospital
  • Sothampton, United Kingdom, SO16 6YD
    • University Hospital Southampton
  • Sutton, United Kingdom, SM2 5PT
    • Royal Marsden Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Birmingham
  • California
    • Duarte, California, United States, 91010
      • City of Hope
    • San Francisco, California, United States, 94143
      • University of California San Francisco
    • Stanford, California, United States, 94305-5623
      • Stanford University Medical Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Winship Cancer Institute Emory University
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria: -

• Documented diagnosis of multiple myeloma according to IMWG diagnostic criteria
• Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
• Measurable disease: Cohort A, Cohort C and Cohort D: Multiple myeloma must be measurable by central laboratory assessment
• A female participant of childbearing potential must have a negative pregnancy test at screening
• Willing and able to adhere to the prohibitions and restrictions specified in this protocol
• Cohorts A and D: received at least 3 prior MM treatment lines of therapy. Prior therapy must include an IMiD, PI, and anti-CD38 monoclonal antibody; Cohort C: received >= 3 prior lines of therapy that included a PI, an IMiD, an anti-CD38 monoclonal antibody, and an anti-B cell maturation antigen (BCMA) treatment (with CART-T cells or an antibody drug conjugate (ADC)

Exclusion Criteria:

• Plasma cell leukemia, Waldenström's macroglobulinemia, POEMS syndrome, or primary amyloid light-chain amyloidosis
• The following medical conditions: Pulmonary compromise requiring supplemental oxygen use to maintain adequate oxygenation, human immunodeficiency virus (HIV) infection, hepatitis B or C infection, stroke or seizure less than or equal to (<=) 6 m, autoimmune disease, uncontrolled systemic infection, cardiac conditions (Myocardial Infarction <= 6 m, stage III-IV congestive heart failure, etc)
• Received any therapy that is targeted to BCMA, with the exception of Cohort C in Part 3
• Prior antitumor therapy, within 21 days (PI or radiotherapy within 14 days, IMiDs within 7 days, Gene modified adoptive cell therapy within 3 months) prior to first dose of study drug
• Toxicities from previous anticancer therapies that have not resolved to baseline or to <= grade 1 (except for alopecia or peripheral neuropathy)
• Received a cumulative dose of corticosteroids equivalent to >=140 mg of prednisone within the 14-day period before the first dose of study drug (does not include pretreatment medication)
• Known active central nervous system (CNS) involvement or exhibits clinical signs of meningeal involvement of multiple myeloma (MM)
• Myelodysplastic syndrome or active malignancies other than relapsed/refractory multiple myeloma with exceptions are: 1) Non-muscle invasive bladder cancer treated within the last 24 months that is considered completely cured 2) Skin cancer (non-melanoma or melanoma) treated within the last 24 months that is considered completely cured. 3) Noninvasive cervical cancer treated within the last 24 months that is considered completely cured. 4) Localized prostate cancer (N0M0) 5) Breast cancer: Adequately treated lobular carcinoma in situ or ductal carcinoma in situ, or history of localized breast cancer and receiving antihormonal agents and considered to have a very low risk of recurrence. 6) Malignancy that is considered cured with minimal risk of recurrence
• Prior allogenic stem cell transplant <=6 months
• Prior autologous stem cell transplant <=12 weeks
• Live, attenuated vaccine within 4 weeks prior to the first dose of teclistamab

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 3: Teclistamab; Participants will receive teclistamab subcutaneously (SC) at recommended Phase 2 dose (RP2D) (Cohort A and Cohort C) and will receive alternative dosing schedule of teclistamab (Cohort D).	Drug: Teclistamab; Teclistamab will be administered SC.; Other Names: JNJ-64007957

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohorts A and C: Overall Response Rate (ORR)	ORR is defined as the proportion of participants who have a partial response (PR) or better according to the International Myeloma Working Group (IMWG) criteria.	Up to 2.9 years
Cohort D: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.	Up to 2.9 years
Cohort D: Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability	An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.	Up to 2.9 years
Cohort D: Number of Participants with AEs by Severity	Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death related to adverse event.	Up to 2.9 years
Cohort D: Number of Participants with Laboratory Abnormalities in Clinical Laboratory Values	Number of participants with laboratory abnormalities in clinical laboratory values (such as hemoglobin, platelets) will be reported.	Up to 2.9 years
Cohort D: Serum Concentration of Teclistamab	Serum concentrations of teclistamab will be reported.	Up to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohorts A and C: Duration of Response (DOR)	DOR 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, as defined in the IMWG criteria, or death due to PD, whichever occurs first.	Up to 2.9 years
Cohorts A and C: Very Good Partial Response (VGPR) or Better Rate	VGPR or better rate is defined as the percentage of patients who achieve a VGPR or better according to IMWG response criteria.	Up to 2.9 years
Cohorts A and C: Cohorts A and C: Complete Response (CR) or Better Rate	CR or better rate is defined as the percentage of patients who achieve a complete response (CR) or better according to IMWG response criteria.	Up to 2.9 years
Cohorts A and C: Stringent Complete Response (sCR) Rate	sCR rate is defined as the percentage of patients who achieve a stringent complete response (sCR) according to IMWG response criteria.	Up to 2.9 years
Cohorts A and C: Time to Response (TTR)	TTR is defined as the time between date of first dose of study drug and the first efficacy evaluation that the participant has met all criteria for PR or better.	Up to 2.9 years
Cohorts A and C: Progression-free Survival (PFS)	PFS is defined as the time from the date of first dose of study drug to the date of first documented disease progression, as defined in the IMWG criteria, or death due to any cause, whichever occurs first.	Up to 2.9 years
Cohorts A and C: Overall Survival (OS)	OS is defined as the time from the date of first dose of study drug to the date of the participant's death.	Up to 2.9 years
Cohorts A and C: Minimal Residual Disease (MRD) Negative Rate	MRD-negative rate is defined as the proportion of participants who achieved MRD-negative status to a threshold of 10^-5 at any timepoint after initial dose of teclistamab and before disease progression or starting subsequent therapy	Up to 2.9 years
Cohorts A and C: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.	Up to 2.9 years
Cohorts A and C: Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability	An SAE is any AE that results in: death, persistent or significant disability/incapacity, requires inpatient hospitalization or prolongation of existing hospitalization, is life-threatening experience, is a congenital anomaly/birth defect and may jeopardize participant and/or may require medical or surgical intervention to prevent one of the outcomes listed above.	Up to 2.9 years
Cohorts A and C: Number of Participants with AEs by Severity	Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening, and Grade 5= Death related to adverse event.	Up to 2.9 years
Cohorts A and C: Number of Participants with Laboratory Abnormalities in Clinical Laboratory Values	Number of participants with laboratory abnormalities in clinical laboratory values (such as hemoglobin, platelets) will be reported.	Up to 2.9 years
Cohorts A and C: Serum Concentration of Teclistamab	Serum concentrations of teclistamab will be reported.	Up to 3 months
Cohorts A and C: Number of Participants with Teclistamab Antibodies	Antibodies to teclistamab will be assessed to evaluate potential immunogenicity.	Up to 2.9 years
Cohorts A and C: Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 item (EORTC QLQ-C30)	The EORTC- QLQ-Core-30 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 recall period is 1 week ("past week"), and responses are reported using a verbal and numeric rating scales. The item and scale scores are transformed to a 0 to 100 scale. A higher score represents greater HRQoL, better functioning, and more (worse) symptoms.	Baseline, up to 2.9 years
Cohorts A and C: Change from Baseline in HRQoL as Assessed by EuroQol Five Dimension Five Level Questionnaire (EQ-5D-5L)	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). The scores for the 5 separate questions are categorical and cannot be analyzed as cardinal numbers.	Baseline, up to 2.9 years
Cohorts A and C: Change from Baseline in HRQoL as Assessed by Patient Global Impression of Severity (PGIS)	The PGIS is a single item that assesses severity of the participant's health state, on a 5-point verbal rating scale. Score ranges from 1 (None) to 5 (Very Severe).	Baseline, up to 2.9 years
Cohorts A and C: Overall Response Rate (ORR) in Participants with High-risk Molecular Features	ORR in participants with high risk is defined as the overall response rate among the high-risk molecular subgroups (del17p, t(4;14), t(14;16), or other high-risk molecular subtypes).	Up to 2.9 years

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Publications and helpful links

General Publications

• Moreau P, Garfall AL, van de Donk NWCJ, Nahi H, San-Miguel JF, Oriol A, Nooka AK, Martin T, Rosinol L, Chari A, Karlin L, Benboubker L, Mateos MV, Bahlis N, Popat R, Besemer B, Martinez-Lopez J, Sidana S, Delforge M, Pei L, Trancucci D, Verona R, Girgis S, Lin SXW, Olyslager Y, Jaffe M, Uhlar C, Stephenson T, Van Rampelbergh R, Banerjee A, Goldberg JD, Kobos R, Krishnan A, Usmani SZ. Teclistamab in Relapsed or Refractory Multiple Myeloma. N Engl J Med. 2022 Aug 11;387(6):495-505. doi: 10.1056/NEJMoa2203478. Epub 2022 Jun 5.

Helpful Links

• Dose Escalation Study of JNJ-64007957, a Humanized BCMA CD3 DuoBody® Antibody, in Participants With Relapsed or Refractory Multiple Myeloma

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2020
• Primary Completion (Estimated): March 13, 2025
• Study Completion (Estimated): September 25, 2025

Study Registration Dates

• First Submitted: September 17, 2020
• First Submitted That Met QC Criteria: September 17, 2020
• First Posted (Actual): September 21, 2020

Study Record Updates

• Last Update Posted (Actual): April 24, 2024
• Last Update Submitted That Met QC Criteria: April 23, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms by Site; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Neoplasms, Plasma Cell; Hematologic Neoplasms; Multiple Myeloma
• Other Study ID Numbers: CR108859; 2016-002122-36 (EudraCT Number); TECLIMMY1001-P3 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinicaltrials/ 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No