A Study of Subcutaneous Daratumumab Regimens in Combination With Bispecific T Cell Redirection Antibodies for the Treatment of Participants With Multiple Myeloma

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Recruiting
CT.gov ID
NCT04108195
Collaborator
(none)
180
Enrollment
25
Locations
2
Arms
45.7
Anticipated Duration (Months)
7.2
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to identify recommended Phase 2 doses (RP2Ds) for each treatment combination (between daratumumab plus talquetamab and teclistamab plus daratumumab with or without pomalidomide) and to characterize the safety of each RP2D for selected treatment combinations.

Detailed Description

Multiple myeloma is a malignant plasma cell disorder characterized by osteolytic lesions, increased susceptibility to infections, hypercalcemia, and renal failure. Overall rationale of study is that daratumumab in combination with talquetamab or teclistamab may lead to enhanced clinical responses in treatment of relapsed or refractory multiple myeloma through multiple mechanisms of action. Daratumumab is human immunoglobulin G1 kappa monoclonal antibody (IgG1k) that binds with high affinity to a unique epitope on cluster of differentiation 38 (CD38) in a variety of hematological malignancies including multiple myeloma. Talquetamab and teclistamab are bispecific T cell redirection antibodies. Talquetamab binds to cluster of differentiation 3 (CD3) receptor complex on T cells and to G protein-coupled receptor family C group 5-member D (GPRC5D), a 7-transmembrane receptor protein on plasma cells and teclistamab binds to human and cynomolgus-CD3 and B cell maturation antigen (BCMA). Purpose of study is to evaluate safety of daratumumab in combination with talquetamab and teclistamab, and to evaluate preliminary antitumor activity of each combination. Study consists of a screening period, treatment period (Part 1: dose escalation and Part 2: dose expansion) and a post treatment follow-up period (after end of treatment and up to 16 weeks after last dose. End of study is defined as last study assessment for last participant in study. Total duration of study is approximately 2.4 years. Efficacy, safety, pharmacokinetics (PK), immunogenicity, and biomarkers will be assessed at specified time points. Participants safety will be monitored throughout study by Study Evaluation Team (SET). SET consists of members of sponsor's study team and participating investigators.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
180 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1b Study of Subcutaneous Daratumumab Regimens in Combination With Bispecific T Cell Redirection Antibodies for the Treatment of Subjects With Multiple Myeloma
Actual Study Start Date :
Feb 21, 2020
Anticipated Primary Completion Date :
Dec 12, 2023
Anticipated Study Completion Date :
Dec 12, 2023

Arms and Interventions

ArmIntervention/Treatment
Experimental: Part 1: Dose Escalation

Participants will be assigned to either a combination of 1) daratumumab plus teclistamab or 2) daratumumab plus talquetamab or 3) daratumumab plus talquetamab plus pomalidomide or 4) daratumumab plus teclistamab plus pomalidomide.

Drug: Daratumumab
Participants will receive daratumumab.
Other Names:
  • JNJ-54767414, Darzalex
  • Drug: Talquetamab
    Participants will receive talquetamab.
    Other Names:
  • JNJ-64407564
  • Drug: Teclistamab
    Participants will receive teclistamab.
    Other Names:
  • JNJ-64007957
  • Drug: Pomalidomide
    Participants will receive pomalidomide.

    Experimental: Part 2: Dose Expansion

    Participants will be treated with the RP2D(s) for selected treatment combinations determined in Part 1 until disease progression, unacceptable toxicity, withdrawal of consent, otherwise deemed necessary by the investigator or the sponsor, or end of study.

    Drug: Daratumumab
    Participants will receive daratumumab.
    Other Names:
  • JNJ-54767414, Darzalex
  • Drug: Talquetamab
    Participants will receive talquetamab.
    Other Names:
  • JNJ-64407564
  • Drug: Teclistamab
    Participants will receive teclistamab.
    Other Names:
  • JNJ-64007957
  • Drug: Pomalidomide
    Participants will receive pomalidomide.

    Outcome Measures

    Primary Outcome Measures

    1. Part 1: Number of Participants With Dose Limiting Toxicity (DLT) [Cycle 1 (Up to 28 days)]

      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: Number of Participants With Dose Limiting Toxicity by Severity [Cycle 1 (Up to 28 days)]

      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.

    3. Part 2: Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAEs) [Up to 48 Weeks]

      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 48 Weeks]

      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.

    Secondary Outcome Measures

    1. Serum Concentration of Daratumumab [Up to 40 Weeks]

      Serum concentration of daratumumab will be assessed.

    2. Serum Concentration of Talquetamab [Up to 40 Weeks]

      Serum concentration of talquetamab will be assessed.

    3. Serum Concentration of Teclistamab [Up to 40 Weeks]

      Serum concentration of teclistamab will be assessed.

    4. Biomarker Assessment of Daratumumab [Up to Cycle 7 Day 1 (each cycle of 28-days)]

      Serum cytokine concentrations will be measured at the time of drug infusion of daratumumab for biomarker assessment.

    5. Biomarker Assessment of Talquetamab [Up to Cycle 7 Day 1 (each cycle of 28-days)]

      Serum cytokine concentrations will be measured at the time of drug infusion of talquetamab for biomarker assessment.

    6. Biomarker Assessment of Teclistamab [Up to Cycle 7 Day 1 (each cycle of 28-days)]

      Serum cytokine concentrations will be measured at the time of drug infusion of teclistamab for biomarker assessment.

    7. Number of Participants With Anti-Drug Antibodies to Daratumumab [Up to 40 Weeks]

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

    8. Number of Participants With Anti-Drug Antibodies to Talquetamab [Up to 40 Weeks]

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

    9. Number of Participants With Anti-Drug Antibodies to Teclistamab [Up to 40 Weeks]

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

    10. Overall Response Rate (ORR) [Up to 48 Weeks]

      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.

    11. Clinical Benefit Rate [Up to 48 Weeks]

      Clinical benefit rate (ORR + minimal response [MR]) is defined as the of participants who have a MR or better according to the IMWG criteria.

    12. Duration of Response (DOR) [Up to 48 Weeks]

      DOR is defined as the time 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.

    13. Time to Response [Up to 48 Weeks]

      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

    • Must have either of the following: a) received at least 3 prior lines of therapy including a proteasome inhibitor (PI) (greater than or equal to [>=] 2 cycles or 2 months of treatment) and an immunomodulatory drug (IMiD) (>=2 cycles or 2 months of treatment) in any order during the treatment or b) disease that is double refractory to a PI and an IMiD

    • Measurable disease at screening as defined by any of the following: Serum monoclonal protein (M-protein) level >= 1.0 grams per deciliter (g/dL) (in non- immunoglobulin G (IgG) myeloma, an M-protein level >=0.5 g/dL); or Urine M-protein level >=200 milligram (mg)/24 hours; or Light chain multiple myeloma: Serum immunoglobulin (Ig) free light chain (FLC) >=10 milligrams per deciliter (mg/dL) and abnormal serum Ig kappa lambda FLC ratio

    • Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 at screening and at Cycle 1, Day 1 predose

    • 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 before the first dose of study drug

    Exclusion Criteria:
    • Treatment in the prior 3 months with an anti- cluster of differentiation 38 (CD38) therapy (example, daratumumab), or discontinuation of a prior anti-CD38 therapy at any time due to an adverse event related to the anti-CD38 therapy

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

    • Active Central nervous system involvement or exhibits clinical signs of meningeal involvement of multiple myeloma. If either is suspected, brain magnetic resonance imaging (MRI) and lumbar cytology are required

    • Seropositive for hepatitis B (defined by a positive test for hepatitis B surface antigen [HBsAg]). Participants with resolved infection must be screened using real-time polymerase chain reaction (PCR) measurement of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) levels. Those who are PCR positive will be excluded

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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1City of Hope National Medical CenterDuarteCaliforniaUnited States91010
    2University of California, San FranciscoSan FranciscoCaliforniaUnited States94143
    3Mount Sinai Medical CenterNew YorkNew YorkUnited States10029
    4Levine Cancer InstituteCharlotteNorth CarolinaUnited States28204
    5Wake Forest Baptist Medical CenterWinston-SalemNorth CarolinaUnited States27157
    6University of PennsylvaniaPhiladelphiaPennsylvaniaUnited States19104
    7Vanderbilt - Ingram Cancer CenterNashvilleTennesseeUnited States37212
    8Medical College Of WisconsinMilwaukeeWisconsinUnited States53226
    9Tom Baker Cancer CentreCalgaryAlbertaCanadaT2N 4N2
    10Vancouver General HospitalVancouverBritish ColumbiaCanadaV5Z 1M9
    11University Health Network (UHN) Princess Margaret Cancer CentreTorontoOntarioCanadaM5G 2M9
    12Universitatsklinikum FreiburgFreiburgGermany79106
    13Universitaetsklinikum Hamburg EppendorfHamburgGermany20246
    14Universitaetsklinikum HeidelbergHeidelbergGermany69120
    15Universitätsklinikum WürzburgWürzburgGermany97080
    16VU Medisch CentrumAmsterdamNetherlands1081 HV
    17UMCGGroningenNetherlands9713 GZ
    18LUMCLeidenNetherlands2333ZA
    19UMCUUtrechtNetherlands3584 CX
    20Hosp. Clinic I Provincial de BarcelonaBarcelonaSpain08036
    21Inst. Cat. Doncologia-H Duran I ReynalsBarcelonaSpain08908
    22Germans Trias I PujolBarcelonaSpain08916
    23Hosp. Univ. Fund. Jimenez DiazMadridSpain28040
    24Clinica Univ. de NavarraPamplonaSpain31008
    25Hosp. Clinico Univ. de SalamancaSalamancaSpain37007

    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:
    NCT04108195
    Other Study ID Numbers:
    • CR108620
    • 2019-000330-19
    • 64407564MMY1002
    First Posted:
    Sep 30, 2019
    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:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Oct 8, 2021