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A Study of Talquetamab in Participants With Relapsed or Refractory Multiple Myeloma

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04634552
Collaborator
(none)
320
Enrollment
83
Locations
3
Arms
62.3
Anticipated Duration (Months)
3.9
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy of talquetamab in participants with relapsed or refractory multiple myeloma at the recommended Phase 2 dose(s) (RP2Ds) (Part 3).

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

Multiple myeloma is a malignant plasma cell disorder characterized by osteolytic lesions, increased susceptibility to infections, hypercalcemia, and renal failure. Talquetamab is a humanized immunoglobulin G4 proline, alanine, alanine (IgG4PAA) bispecific antibody designed to target G protein-coupled receptor family C group 5-member D (GPRC5D) and the CD3 molecule found on T lymphocytes (T cell). This study consists 3 periods: screening phase (up to 28 days), treatment phase (start of study drug administration and continues until the completion of the end of treatment [EOT (30 days (+ 7 days)] visit); and a post-treatment follow-up phase (until the end of study unless the participant has died, is lost to follow up or has withdrawn consent). Total duration of study is up to 2 years (after the last participant receives their first dose). Safety, pharmacokinetics (PK), laboratory tests, and questionnaire will be assessed at specified time points during this study. Participants safety and study conduct will be monitored throughout the study. The corresponding study (NCT03399799) is the Phase 1 part of the study and TALMMY1001- Part 3 is the Phase 2 part of the study.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
320 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1/2, First-in-Human, Open-Label, Dose Escalation Study of Talquetamab, a Humanized GPRC5D x CD3 Bispecific Antibody, in Subjects With Relapsed or Refractory Multiple Myeloma
Actual Study Start Date :
Feb 1, 2021
Anticipated Primary Completion Date :
Aug 27, 2023
Anticipated Study Completion Date :
Apr 13, 2026

Arms and Interventions

Arm Intervention/Treatment
Experimental: Part 3: Cohort A (Talquetamab)

Cohort A will enroll participants with multiple myeloma who have previously received greater than or equal to (>=) 3 prior lines of therapy and have not been exposed to T cell redirection therapies. Participants will receive talquetamab subcutaneously (SC) at a recommended Phase 2 dose (RP2D) selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study.

Drug: Talquetamab
Talquetamab will be administered SC until disease progression.
Other Names:
  • JNJ-64407564

    		•
    Experimental: Part 3: Cohort B (Talquetamab)

    Cohort B will enroll participants with multiple myeloma who have previously received >= 3 prior lines of therapy and have been exposed to T cell redirection therapies. Participants will receive talquetamab subcutaneously (SC) at a recommended Phase 2 dose (RP2D) selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study.

    Drug: Talquetamab
    Talquetamab will be administered SC until disease progression.
    Other Names:
  • JNJ-64407564

    		•
    Experimental: Part 3: Cohort C (Talquetamab)

    Cohort C will enroll participants with multiple myeloma who have previously received >= 3 prior lines of therapy and have not been exposed to T cell redirection therapies. Participants will receive talquetamab SC biweekly at a RP2D selected after review of safety, efficacy, PK, and pharmacodynamic data from Part 1 and Part 2 of this study.

    Drug: Talquetamab
    Talquetamab will be administered SC until disease progression.
    Other Names:
  • JNJ-64407564

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Overall Response Rate (ORR) [Up to 2 years and 10 months]

      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 years and 10 months]

      DOR is defined as time from date of initial documentation of a response (PR or better) to date of first documented evidence of progressive disease (PD), per IMWG criteria, or death due to PD, whichever occurs first.

    2. Very Good Partial Response (VGPR) or Better Rate [Up to 2 years and 10 months]

      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 years and 10 months]

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

    4. Stringent Complete Response (sCR) Rate [Up to 2 years and 10 months]

      sCR rate is defined as the percentage of patients who achieve sCR according to IMWG response criteria.

    5. Time to Response (TTR) [Up to 2 years and 10 months]

      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 years and 10 months]

      PFS is defined as time from date of first dose of study drug to date of first documented PD, per IMWG criteria, or death due to any cause, whichever occurs first.

    7. Overall Survival (OS) [Up to 2 years and 10 months]

      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 years and 10 months]

      MRD negativity rate is measured only for participants who achieve at least a CR but is reported based on all treated similar to the other response data.

    9. Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability [Up to 2 years and 10 months]

      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 years and 10 months]

      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, 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 years and 10 months]

      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 Abnormalities in Clinical Laboratory Values [Up to 2 years and 10 months]

      Number of participants with abnormalities in clinical laboratory values (such as hematology, serum chemistry and coagulation) will be reported.

    13. Serum Concentration of Talquetamab [Up to 2 years and 10 months]

      Serum samples will be analyzed to determine concentrations of talquetamab.

    14. Number of Participants with Talquetamab Antibodies [Up to 2 years and 10 months]

      Antibodies to talquetamab 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 years and 10 months]

      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 years and 10 months]

      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 years and 10 months]

      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 years and 10 months]

      ORR in participants with high risk is defined as the overall response rate among the high risk molecular subgroups 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 initial diagnosis of multiple myeloma according to international myeloma working group (IMWG) diagnostic criteria

    • Part 3: Measurable disease cohort A, cohort B, and cohort C: multiple myeloma must be measurable by central laboratory assessment

    • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 2

    • Women of childbearing potential must have a negative pregnancy test at screening and prior to the first dose of study drug using a highly sensitive pregnancy test either serum (beta human chorionic gonadotropin [hCG]) or urine

    • Willing and able to adhere to the prohibitions and restrictions specified in this protocol

    Exclusion Criteria:

    • Part 3 only: Cohort A and Cohort C only: exposed to a CAR-T or T cell redirection therapy at any time. Cohort B: T cell redirection therapy within 3 months

    • Vaccinated with live, attenuated vaccine within 4 weeks or as recommended by the product manufacturer prior to the first dose, during treatment, or within 100 days of the last dose of talquetamab

    • Toxicities from previous anticancer therapies should have resolved to baseline levels or to Grade 1 or less except for alopecia or peripheral neuropathy

    • Received a cumulative dose of corticosteroids equivalent to >= 140 milligram (mg) of prednisone within the 14-day period before the first dose of study drug (does not include pretreatment medication)

    • Stroke or seizure within 6 months prior to signing the informed consent form (ICF)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 University of Alabama Birmingham Birmingham Alabama United States 35294
    2 The University of Arizona Cancer Center Tucson Arizona United States 85719
    3 University of Arkansas for Medical Sciences Little Rock Arkansas United States 72205
    4 City of Hope Duarte California United States 91010
    5 Emory University - Winship Cancer Institute Atlanta Georgia United States 30322
    6 University of Chicago Chicago Illinois United States 60637
    7 Norton Cancer Institute Louisville Kentucky United States 40207
    8 University of Michigan Health System Ann Arbor Michigan United States 48109
    9 Washington University School of Medicine Saint Louis Missouri United States 63110
    10 NYU Langone Health New York New York United States 10016
    11 Mount Sinai Medical Center New York New York United States 10023
    12 University of Rochester Medical Center Rochester New York United States 14642
    13 Levine Cancer Institute Charlotte North Carolina United States 28204
    14 The Ohio State University Wexner Medical Center - James Cancer Hospital Columbus Ohio United States 43210
    15 Providence Portland Medical Center Portland Oregon United States 97213
    16 Sarah Cannon Research Institute Nashville Tennessee United States 37203
    17 University of Texas, MD Anderson Cancer Center Houston Texas United States 77030
    18 UCL - Saint Luc Brussels Belgium 1200
    19 UZ Antwerpen Edegem Belgium 2650
    20 UZ Leuven Leuven Belgium 3000
    21 CHU de Liège - Domaine Universitaire du Sart Tilman Liège Belgium 4000
    22 Peking University Third Hospital Beijing China 100191
    23 Second Affiliated Hospital of Army Medical University Chongqing China 400037
    24 Sun Yat-Sen University Cancer Center Guangzhou China 510060
    25 First affiliated Hospital of Zhejiang University Hangzhou China 310003
    26 First Affiliated Hospital, SooChow University Su Zhou China 215006
    27 Institute of Hematology & Blood Disease Hospital Chinese Academy of Medical Science Tianjin China 300320
    28 First Affiliated Hospital of Xi'an Jiaotong University School of Medicine Xi'an China 710061
    29 CHU Henri Mondor Creteil France 94000
    30 CHU de Montpellier, Hopital Saint-Eloi Montpellier France 34295
    31 C.H.U. Hotel Dieu - France Nantes France 44093
    32 CHU de Bordeaux - Hôpital Haut-Lévêque Pessac cedex France 33604
    33 Centre hospitalier Lyon-Sud Pierre Benite cedex France 69495
    34 Pôle IUC Oncopole CHU Toulouse cedex 9 France 31059
    35 Charite Campus Benjamin Franklin Berlin Germany 12203
    36 Universitatsklinikum Freiburg Freiburg Germany 79106
    37 Medizinische Hochschule Hannover Hannover Germany 30625
    38 Universitaetsklinikum Heidelberg Heidelberg Germany 69120
    39 Universitaetsklinikum Muenster Muenster Germany 48149
    40 Klinikum Großhadern der Ludwig-Maximilians-Universität München Germany 81377
    41 Universitätsklinikum Würzburg Würzburg Germany 97080
    42 Rambam Medical Center Haifa Israel 31096
    43 Carmel Medical Center Haifa Israel 3436212
    44 Hadassah Medical Center Jerusalem Israel 91120
    45 Sheba Medical Center Ramat Gan Israel 52621
    46 Tel Aviv Sourasky Medical Center Tel Aviv Israel 64239
    47 Kameda General Hospital Chiba Japan 296-8602
    48 Fukuoka University Hospital Fukuoka Japan 814-0180
    49 Ogaki Municipal Hospital Gifu Japan 503-8502
    50 Kobe City Medical Center General Hospital Hyogo Japan 650-0047
    51 Dokkyo Medical University Saitama Medical Center Koshigaya Japan 343-8555
    52 Kumamoto University Hospital Kumamoto Japan 860-8556
    53 Kurashiki Central Hospital Kurashiki Japan 710-8602
    54 National Hospital Organization Matsumoto Medical Center Matsumoto Japan 399-8701
    55 Nagoya City University Hospital Nagoya Japan 467-8602
    56 National Hospital Organization Okayama Medical Center Okayama Japan 701-1192
    57 Japanese Red Cross Osaka Hospital Osaka Japan 543-8555
    58 Iwate Medical University Hospital Shiwa-gun Japan 028-3695
    59 Chonnam National University Hwasun Hospital Jeollanam-do Korea, Republic of 58128
    60 Seoul National University Hospital Seoul Korea, Republic of 03080
    61 Severance Hospital, Yonsei University Health System Seoul Korea, Republic of 03722
    62 Asan Medical Center Seoul Korea, Republic of 05505
    63 Samsung Medical Center Seoul Korea, Republic of 06351
    64 The Catholic University of Korea, Seoul St. Mary's Hospital Seoul Korea, Republic of 06591
    65 VU Medisch Centrum Amsterdam Netherlands 1081 HV
    66 UMCU Utrecht Netherlands 3584 CX
    67 Uniwersyteckie Centrum Kliniczne Gdansk Poland 80-214
    68 Narodowy Instytut Onkologii im.Marii Sklodowskiej Curie Panstwowy Instytut BadawczyOddz. w Gliwicach Gliwice Poland 44102
    69 Centrum Onkologii Ziemi Lubelskiej im. św. Jana z Dukli Lublin Poland 20090
    70 Szpital Kliniczny Przemienienia Panskiego Uniwersytetu Medycznego im. Karola Marcinkowskiego Poznan Poland 60-569
    71 Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy Warszawa Poland 02-781
    72 Uniwersytecki Szpital Kliniczny im. Jana Mikulicza-Radeckiego we Wroclawiu Wroclaw Poland 50-367
    73 Hosp. Univ. Germans Trias I Pujol Badalona Spain 08916
    74 Hosp. Univ. Vall D Hebron Barcelona Spain 08035
    75 Inst. Cat. Doncologia-H Duran I Reynals Barcelona Spain 8908
    76 Hosp. Univ. Fund. Jimenez Diaz Madrid Spain 28040
    77 Hosp. Univ. 12 de Octubre Madrid Spain 28041
    78 Hosp. Univ. Virgen de La Arrixaca Murcia Spain 30120
    79 Clinica Univ. de Navarra Pamplona Spain 31008
    80 Hosp. Quiron Madrid Pozuelo Pozuelo de Alarcon Spain 28223
    81 Hosp. Clinico Univ. de Salamanca Salamanca Spain 37007
    82 Hosp. Univ. Marques de Valdecilla Santander Spain 39008
    83 Hosp. Virgen Del Rocio Sevilla Spain 41013

    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:
    NCT04634552
    Other Study ID Numbers:
    • CR108920
    • 2017-002400-26
    • TALMMY1001-PT3
    First Posted:
    Nov 18, 2020
    Last Update Posted:
    Aug 12, 2022
    Last Verified:
    Aug 1, 2022
    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
    Keywords provided by Janssen Research & Development, LLC
    Multiple Myeloma
    Additional relevant MeSH terms:
    Multiple Myeloma
    Neoplasms, Plasma Cell
    Hematologic Neoplasms

    Study Results

    No Results Posted as of Aug 12, 2022