A Study of the Combination of Talquetamab and Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04586426
Collaborator
(none)
56
Enrollment
13
Locations
2
Arms
29.8
Anticipated Duration (Months)
4.3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to identify the recommended Phase 2 regimen(s) (RP2R[s]) and schedule for the study treatment (Part 1) and to characterize the safety of the RP2R(s) for the study treatment (Part 2). The RP2R(s) will describe the combination doses and schedules of (tal+tec+dara) the treatment combinations to be pursued in Phase 2.

Condition or DiseaseIntervention/TreatmentPhase
Phase 1

Detailed Description

Multiple myeloma is a malignant plasma cell disorder characterized by production of monoclonal proteins (M proteins), which are comprised of pathologic immunoglobulins (Ig) or fragments of such, which have subsequently lost their normal function. Talquetamab is a humanized 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). Teclistamab is a humanized IgG4PAA bispecific antibody designed to target B cell maturation antigen (BCMA) and the CD3 molecule found on T cells. Daratumumab is a human IgG1ĸ monoclonal antibody that binds with high affinity to a unique epitope on cluster of differentiation 38 (CD38) in a variety of hematological malignancies including multiple myeloma. Rationale for combining talquetamab and teclistamab is that, these agents promote the activation of T cells and induce myeloma cell lysis mediated by secreted perforin and various granzymes stored in the secretory vesicles of cytotoxic T cells and daratumumab induces lysis of CD38-expressing tumor cells by a number of mechanisms, including complement-dependent cytotoxicity (CDC), antibody dependent cell-mediated cytotoxicity (ADCC), and antibody-dependent cellular phagocytosis (ADCP), through activation of complement proteins, natural killer (NK) cells, and macrophages, respectively. 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] visit); and a post-treatment follow-up phase (after end of treatment and up to 16 weeks after last dose of study drug(s) for each participant). End of study is defined as last study assessment for last participant in study. Total duration of study is up to 1 year and 6 months. Efficacy, safety, pharmacokinetics (PK), immunogenicity, and biomarkers will be assessed at specified time points during this study. Participants safety and study conduct will be monitored throughout the study.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
56 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1b Dose Escalation Study of the Combination of the Bispecific T Cell Redirection Antibodies Talquetamab and Teclistamab in Participants With Relapsed or Refractory Multiple Myeloma
Actual Study Start Date :
Dec 15, 2020
Anticipated Primary Completion Date :
Nov 1, 2021
Anticipated Study Completion Date :
Jun 9, 2023

Arms and Interventions

ArmIntervention/Treatment
Experimental: Part 1: Dose Escalation

Participants will receive tec+tal with or without daratumumab in 28-day cycles following initial step-up doses.

Drug: Talquetamab
Talquetamab will be administered by subcutaneous (SC) injection.
Other Names:
  • JNJ-64407564
  • Drug: Teclistamab
    Teclistamab will be administered by SC injection.
    Other Names:
  • JNJ-64007957
  • Drug: Daratumumab
    Daratumumab will be administered by SC injection.

    Experimental: Part 2: Dose Expansion

    Participants will receive treatment doses (combination of tal+tec and dara+tal+tec regimens) which will be determined by the RP2R(s) of the study treatment identified in Part 1.

    Drug: Talquetamab
    Talquetamab will be administered by subcutaneous (SC) injection.
    Other Names:
  • JNJ-64407564
  • Drug: Teclistamab
    Teclistamab will be administered by SC injection.
    Other Names:
  • JNJ-64007957
  • Drug: Daratumumab
    Daratumumab will be administered by SC injection.

    Outcome Measures

    Primary Outcome Measures

    1. Part 1: Number of Participants with Dose Limiting Toxicity (DLT) [Up to 1 year and 6 months]

      The dose limiting toxicities are based on drug related adverse events and defined as any of the following events: hematological or non-hematological toxicity of grade 3 or higher.

    2. Part 1: Severity of DLT as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) [Up to 1 year and 6 months]

      Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. 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.

    3. Part 2: Number of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) as a Measure of Safety and Tolerability [Up to 1 year and 6 months]

      An AE is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. 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 suspects transmission of any infectious agent via a medicinal product.

    4. Part 2: Number of Participants with Adverse Events and SAEs by Severity [Up to 1 year and 6 months]

      Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. 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.

    Secondary Outcome Measures

    1. Part 1 and Part 2: Serum Concentration of Talquetamab [Up to 1 year and 6 months]

      Serum samples will be analyzed to determine concentrations of talquetamab using a validated, specific, and sensitive immunoassay method.

    2. Part 1 and Part 2: Serum Concentration of Teclistamab [Up to 1 year and 6 months]

      Serum samples will be analyzed to determine concentrations of teclistamab using a validated, specific, and sensitive immunoassay method.

    3. Part 1 and Part 2: Serum Concentration of Daratumumab [Up to 1 year and 6 months]

      Serum samples will be analyzed to determine concentrations of daratumumab using a validated, specific, and sensitive immunoassay method.

    4. Part 1 and Part 2: Number of Participants with Anti-Drug Antibodies to Talquetamab [Up to 1 year and 6 months]

      Number of participants with anti-drug antibodies to talquetamab will be assessed.

    5. Part 1 and Part 2: Number of Participants with Anti-Drug Antibodies to Teclistamab [Up to 1 year and 6 months]

      Number of Participants with anti-drug antibodies to teclistamab will be assessed.

    6. Part 1 and Part 2: Number of Participants with Anti-Drug Antibodies to Daratumumab [Up to 1 year and 6 months]

      Number of Participants with anti-drug antibodies to daratumumab will be assessed.

    7. Part 1 and Part 2: Overall Response Rate (ORR) [Up to 1 year and 6 months]

      ORR is defined as the percentage of participants who have a partial response (PR) or better according to the International Myeloma Working Group (IMWG) criteria.

    8. Part 1 and Part 2: Very Good Partial Response (VGPR) or Better Response Rate [Up to 1 year and 6 months]

      VGPR or better response rate (sCR+CR+VGPR) is defined as the percentage of participants who achieve a VGPR or better response according to the IMWG criteria.

    9. Part 1 and Part 2: Complete Response (CR) or Better Response Rate [Up to 1 year and 6 months]

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

    10. Part 1 and Part 2: Stringent Complete Response (sCR) Rate [Up to 1 year and 6 months]

      sCR rate is defined as the percentage of participants who achieve a sCR according to the IMWG criteria.

    11. Part 1 and Part 2: Duration of Response (DOR) [Up to 1 year and 6 months]

      DOR will be calculated among responders (with PR or better) 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.

    12. Part 1 and Part 2: Time to Response [Up to 1 year and 6 months]

      Time to response 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.

    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 based on documented medical history

    • Participant could not tolerate or has disease that is relapsed or refractory to established therapies, including the last line of therapy (except as noted in point 'a' and 'b'). (a) For cohorts without daratumumab, prior lines of therapy must include a proteasome inhibitor (PI) (example, bortezomib, carfilzomib, ixazomib), an immunomodulatory drug (IMiD) (example, thalidomide, lenalidomide, pomalidomide), and an anti-CD38 therapy (example, daratumumab, isatuximab) in any order. (b) For cohorts with daratumumab, prior lines of therapy must include a PI (example, bortezomib, carfilzomib, ixazomib) and an IMiD (example, thalidomide, lenalidomide, pomalidomide). Treatment with an anti-CD38 therapy (example, daratumumab) is allowed greater than equal to (>=) 90 days prior to study treatment if the participant did not discontinue prior treatment due to adverse events related to anti-CD38 therapy

    • Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 at screening and immediately before the start of study drug administration

    • Women of childbearing potential must have a negative highly-sensitive serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test (less than [<] 5 international units per milliliter [IU/mL]) at screening and a negative urine or serum pregnancy test within 24 hours prior to the first step-up dose and the first dose of each treatment cycle

    • Men must agree not to donate sperm for reproduction during the study and for a minimum 100 days after receiving the last dose of study treatment

    Exclusion Criteria:
    • Prior anticancer therapy as follows: a) targeted therapy, epigenetic therapy, or treatment with an investigational treatment or an invasive investigational medical device within 21 days or at least 5 half-lives, whichever is less; b) monoclonal antibody treatment for multiple myeloma within 21 days; c) cytotoxic therapy within 21 days; d) proteasome inhibitor (PI) therapy within 14 days; e) immunomodulatory drug (IMiD) therapy within 7 days; f) radiotherapy within 21 days. However, if the radiation portal covered less than or equal to (<=) of the bone marrow reserve, the participant is eligible irrespective of the end date of radiotherapy; g) gene modified adoptive cell therapy (example, chimeric antigen receptor modified T cells, natural killer [NK] cells) within 3 months

    • A cumulative dose of corticosteroids equivalent to more than or equal to (>=) 140 milligram (mg) of prednisone within 14 days

    • Live, attenuated vaccine within 4 weeks prior to first dose of study drug unless approved by sponsor

    • Active hepatitis C infection as measured by positive hepatitis C virus (HCV)-RNA testing. Participants with a history of HCV antibody positivity must undergo HCV RNA testing

    • Known allergies, hypersensitivity, or intolerance to daratumumab, talquetamab, teclistamab, or their excipients

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Alberta Health ServicesEdmontonAlbertaCanadaT6G 1Z2
    2McGill University Health CentreMontrealQuebecCanadaH4A 3J1
    3Hadassah Medical CenterJerusalemIsrael91120
    4Sheba Medical CenterRamat GanIsrael52621
    5Tel-Aviv Sourasky Medical CenterTel-AvivIsrael64239
    6Seoul National University HospitalSeoulKorea, Republic of03080
    7Samsung Medical CenterSeoulKorea, Republic of06351
    8The Catholic University of Korea, Seoul St. Mary's HospitalSeoulKorea, Republic of06591
    9Hosp. Univ. Germans Trias I PujolBadalonaSpain08916
    10Hosp. Univ. Fund. Jimenez DiazMadridSpain28040
    11Clinica Univ. de NavarraPamplonaSpain31008
    12Hosp. Clinico Univ. de SalamancaSalamancaSpain37007
    13Hosp. Univ. Marques de ValdecillaSantanderSpain39008

    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:
    NCT04586426
    Other Study ID Numbers:
    • CR108901
    • 2019-004124-38
    • 64007957MMY1003
    First Posted:
    Oct 14, 2020
    Last Update Posted:
    Oct 8, 2021
    Last Verified:
    Oct 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 8, 2021