MajesTEC-1: A Study of Teclistamab, in Participants With Relapsed or Refractory Multiple Myeloma

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04557098
Collaborator
(none)
192
Enrollment
70
Locations
1
Arm
51.4
Anticipated Duration (Months)
2.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

Detailed Description

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

Study Design

Study Type:
Interventional
Anticipated Enrollment :
192 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Actual Study Start Date :
Sep 17, 2020
Anticipated Primary Completion Date :
Apr 23, 2023
Anticipated Study Completion Date :
Dec 30, 2024

Arms and Interventions

ArmIntervention/Treatment
Experimental: Part 3: Teclistamab

Participants in all cohorts will receive teclistamab SC at an RP2D.

Drug: Teclistamab
Teclistamab will be administered SC.
Other Names:
  • JNJ-64007957
  • Outcome Measures

    Primary Outcome Measures

    1. Overall Response Rate (ORR) [Up to 2.9 years]

      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.

    Secondary Outcome Measures

    1. Duration of Response (DOR) [Up to 2.9 years]

      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.

    2. Very Good Partial Response (VGPR) or Better Rate [Up to 2.9 years]

      VGPR or better rate is defined as the percentage of patients who achieve a VGPR or better according to IMWG response criteria.

    3. Complete Response (CR) or Better Rate [Up to 2.9 years]

      CR or better rate is defined as the percentage of patients who achieve a complete response (CR) or better according to IMWG response criteria.

    4. Stringent Complete Response (sCR) Rate [Up to 2.9 years]

      sCR rate is defined as the percentage of patients who achieve a stringent complete response (sCR) according to IMWG response criteria.

    5. Time to Response (TTR) [Up to 2.9 years]

      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.

    6. Progression-free Survival (PFS) [Up to 2.9 years]

      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.

    7. Overall Survival (OS) [Up to 2.9 years]

      OS is defined as the time from the date of first dose of study drug to the date of the participant's death.

    8. Minimal Residual Disease (MRD) Negative Rate [Up to 2.9 years]

      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

    9. Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability [Up to 2.9 years]

      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.

    10. Number of Participants with Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability [Up to 2.9 years]

      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.

    11. Number of Participants with AEs by Severity [Up to 2.9 years]

      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.

    12. Number of Participants with Laboratory Abnormalities in Clinical Laboratory Values [Up to 2.9 years]

      Number of participants with laboratory abnormalities in clinical laboratory values (such as hemoglobin, platelets) will be reported.

    13. Serum Concentration of Teclistamab [Up to 3 months]

      Serum concentrations of teclistamab will be reported.

    14. Number of Participants with Teclistamab Antibodies [Up to 2.9 years]

      Antibodies to teclistamab will be assessed to evaluate potential immunogenicity.

    15. 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) [Baseline, up to 2.9 years]

      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.

    16. Change from Baseline in HRQoL as Assessed by EuroQol Five Dimension Five Level Questionnaire (EQ-5D-5L) [Baseline, up to 2.9 years]

      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.

    17. Change from Baseline in HRQoL as Assessed by Patient Global Impression of Severity (PGIS) [Baseline, up to 2.9 years]

      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).

    18. Overall Response Rate (ORR) in Participants with High-risk Molecular Features [Up to 2.9 years]

      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).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No

    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: Multiple myeloma must be measurable by central laboratory assessment

    • Women 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

    • Cohort A: 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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1University of Alabama at BirminghamBirminghamAlabamaUnited States35294
    2Mayo Clinic Cancer Center-ScottsdalePhoenixArizonaUnited States85054
    3City of HopeDuarteCaliforniaUnited States91010
    4University of California, San FranciscoSan FranciscoCaliforniaUnited States94143
    5Stanford University Medical CenterStanfordCaliforniaUnited States94305-5623
    6Yale UniversityNew HavenConnecticutUnited States06510
    7Mayo Clinic in FloridaJacksonvilleFloridaUnited States32224
    8Winship Cancer Institute Emory UniversityAtlantaGeorgiaUnited States30322
    9University of KansasWestwoodKansasUnited States66205
    10Dana-Farber Cancer InstituteBostonMassachusettsUnited States02215-5418
    11University of Michigan Comprehensive Cancer CenterAnn ArborMichiganUnited States48109
    12Barbara Ann Karmanos Cancer InstituteDetroitMichiganUnited States48201
    13Hackensack University Medical CenterHackensackNew JerseyUnited States07601
    14Icahn School of Medicine at Mount SinaiNew YorkNew YorkUnited States10029
    15Memorial Sloan-Kettering Cancer CenterNew YorkNew YorkUnited States10065
    16Mayo Clinic Cancer CenterRochesterNew YorkUnited States55905
    17Levine Cancer InstituteCharlotteNorth CarolinaUnited States28204
    18Duke University Medical CenterDurhamNorth CarolinaUnited States27710
    19The Ohio State University Wexner Medical Center - James Cancer HospitalColumbusOhioUnited States43210
    20University of PennsylvaniaPhiladelphiaPennsylvaniaUnited States19104
    21University of Pittsburgh Medical CenterPittsburghPennsylvaniaUnited States15232
    22Vanderbilt - Ingram Cancer CenterNashvilleTennesseeUnited States37212
    23University of Texas Southwestern Medical CenterDallasTexasUnited States75390
    24Huntsman Cancer InstituteSalt Lake CityUtahUnited States84112
    25Fred Hutchinson Cancer Research CenterSeattleWashingtonUnited States98109
    26Medical College Of WisconsinMilwaukeeWisconsinUnited States53226
    27Universitair Ziekenhuis Gent - UZ GENTGentBelgium9000
    28Universitaire Ziekenhuizen LeuvenLeuvenBelgium3000
    29Tom Baker Cancer CentreCalgaryAlbertaCanadaT2N 4N2
    30Cross Cancer InstituteEdmontonAlbertaCanadaT6G 1Z2
    31University Health Network (UHN) Princess Margaret Cancer CentreTorontoOntarioCanadaM5G 2M9
    32McGill University Health CentreMontrealQuebecCanadaH4A 3J1
    33West China Hospital, Si Chuan UniversityChengduChina610041
    34Sun Yat -Sen University Cancer CenterGuangzhouChina510060
    35First affiliated Hospital of Zhejiang UniversityHangzhouChina310003
    36Shanghai Changzheng HospitalShanghaiChina200003
    37The Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'anChina710004
    38Centre Hospitalier Régional Universitaire de Lille, Hôpital Claude HuriezLille CedexFrance59000
    39C.H.U. Hotel Dieu - FranceNantesFrance44093
    40Centre Hospitalier Lyon SudPierre BeniteFrance69495
    41CHRU Hôpital Jean BernardPoitiersFrance86021
    42Pôle IUC Oncopole CHUToulouse cedex 9France31059
    43CHRU Hôpital BretonneauToursFrance37044
    44Universitätsklinikum Carl-Gustav-Carus DresdenDresdenGermany01307
    45Universitaetsklinikum Hamburg EppendorfHamburgGermany20246
    46Universitaetsklinikum HeidelbergHeidelbergGermany69120
    47Universitaetsklinikum KoelnKoelnGermany50937
    48Universitatsklinikum LeipzigLeipzigGermany04103
    49Universitaetsklinikum Tuebingen der Eberhard-Karls-Universitaet, Abteilung fuer Innere Medizin II,TübingenGermany72076
    50Universitätsklinikum WürzburgWürzburgGermany97080
    51Azienda Ospedaliera Papa Giovanni XXIIIBergamoItaly24127
    52Istituto di Ematologia Seràgnoli azienda ospedaliera univeristaria Policlinico S.Orsola-MalpighiBolognaItaly40138
    53Fondazione IRCCS Istituto Nazionale dei TumoriMilanoItaly20133
    54A.O.U. Citta della Salute e della Scienza di Torino - Presidio MolinetteTurinItaly10126
    55VU Medisch CentrumAmsterdamNetherlands1081 HV
    56Universitair Medisch Centrum GroningenGroningenNetherlands9713 GZ
    57Erasmus MCRotterdamNetherlands3075 EA
    58Hosp. Univ. Germans Trias I PujolBadalonaSpain08916
    59Hosp. Clinic I Provincial de BarcelonaBarcelonaSpain08036
    60Hosp. Univ. 12 de OctubreMadridSpain28041
    61Clinica Univ. de NavarraPamplonaSpain31008
    62Hosp. Quiron Madrid PozueloPozuelo de AlarconSpain28223
    63Hosp. Clinico Univ. de SalamancaSalamancaSpain37007
    64Hosp. Univ. Marques de ValdecillaSantanderSpain39008
    65Sahlgrenska University HospitalGöteborgSweden413 45
    66Skane University HospitalLundSweden221 85
    67Haematology Centre, R 51StockholmSwedenSE-141 86
    68University College HospitalLondonUnited KingdomNW1 2PG
    69University Hospital SouthamptonSothamptonUnited KingdomSO16 6YD
    70Royal Marsden HospitalSuttonUnited KingdomSM2 5PT

    Sponsors and Collaborators

    • Janssen Research & Development, LLC

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Janssen Research & Development, LLC
    ClinicalTrials.gov Identifier:
    NCT04557098
    Other Study ID Numbers:
    • CR108859
    • 2016-002122-36
    • TECLIMMY1001-P3
    First Posted:
    Sep 21, 2020
    Last Update Posted:
    Dec 3, 2021
    Last Verified:
    Dec 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Dec 3, 2021