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

NCT04108195

Description:

The purpose of this study is to identify recommended Phase 2 doses (RP2Ds) and schedules for each combination (combination 1: daratumumab and JNJ-64407564 [anti-GPRC5DxCD3] or combination 2: daratumumab and JNJ-64007957 [anti-BCMAxCD3]) and to characterize the safety of each RP2D for each combination.

Related Conditions:
  • Multiple Myeloma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: CR108620
  • SECONDARY ID: 2019-000330-19
  • SECONDARY ID: 64407564MMY1002
  • NCT ID: NCT04108195

Conditions

  • Multiple Myeloma

Interventions

DrugSynonymsArms
DaratumumabJNJ-54767414, DarzalexPart 1: Dose Escalation
JNJ-64407564Anti-GPRC5DxCD3Part 1: Dose Escalation
JNJ-64007957Anti-BCMAxCD3Part 1: Dose Escalation

Purpose

The purpose of this study is to identify recommended Phase 2 doses (RP2Ds) and schedules for each combination (combination 1: daratumumab and JNJ-64407564 [anti-GPRC5DxCD3] or combination 2: daratumumab and JNJ-64007957 [anti-BCMAxCD3]) and to characterize the safety of each RP2D for each combination.

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 JNJ-64407564 [anti-GPRC5DxCD3] or
      JNJ-64007957 [anti-BCMAxCD3] 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. JNJ-64407564 (anti-GPRC5DxCD3) and JNJ-64007957 (anti-BCMAxCD3)
      are bispecific T cell redirection antibodies. JNJ-64407564 (anti-GPRC5DxCD3) 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
      JNJ-64007957 (anti-BCMAxCD3) binds to human and cynomolgus-CD3 and B cell maturation antigen
      (BCMA). Purpose of study is to evaluate safety of daratumumab in combination with bispecific
      T cell redirecting antibodies, and to evaluate 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.
    

Trial Arms

NameTypeDescriptionInterventions
Part 1: Dose EscalationExperimentalParticipants will be assigned to either daratumumab and JNJ-64407564 (Combination 1) or daratumumab and JNJ-64007957 (Combination 2) to receive daratumumab Dose 1 subcutaneously (SC) in 28-day cycles (weekly in Cycles 1-2, biweekly in Cycles 3-6, and every 4 weeks thereafter) in combination with JNJ-64407564 or JNJ-64007957 intravenously (IV) once weekly in 28‑day cycles, in a step-up dosing fashion in Cycle 1 until the treatment dose is reached, to establish the recommended Phase 2 dose(s) RP2D(s) of each combination.
  • Daratumumab
  • JNJ-64407564
  • JNJ-64007957
Part 2: Dose ExpansionExperimentalParticipants will be treated with the RP2D(s) for each combination 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.
  • Daratumumab
  • JNJ-64407564
  • JNJ-64007957

Eligibility Criteria

        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 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 free light chain >=10 milligrams
             per deciliter (mg/dL) and abnormal serum immunoglobulin kappa lambda free light chain
             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 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 [Beta-hCG]) or urine

        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

          -  Central nervous system involvement or exhibits clinical signs of meningeal involvement
             of multiple myeloma. If either is suspected, whole body 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

          -  Seropositive for hepatitis C (except in the setting of a sustained virologic response
             [SVR], defined as aviremia at least 12 weeks after completion of antiviral therapy)
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1: Number of Participants With Dose Limiting Toxicity (DLT)
Time Frame:Cycle 1 (Up to 28 days)
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Serum Concentration of Daratumumab
Time Frame:Up to 40 Weeks
Safety Issue:
Description:Serum concentration of daratumumab will be assessed.
Measure:Serum Concentration of JNJ-64407564
Time Frame:Up to 40 Weeks
Safety Issue:
Description:Serum concentration of JNJ-64407564 will be assessed.
Measure:Serum Concentration of JNJ-64007957
Time Frame:Up to 40 Weeks
Safety Issue:
Description:Serum concentration of JNJ-64007957 will be assessed.
Measure:Biomarker Assessment of Daratumumab
Time Frame:Up to Cycle 7 Day 1 (each cycle of 28-days)
Safety Issue:
Description:Serum cytokine concentrations will be measured at the time of drug infusion of daratumumab for biomarker assessment.
Measure:Biomarker Assessment of JNJ-64407564
Time Frame:Up to Cycle 7 Day 1 (each cycle of 28-days)
Safety Issue:
Description:Serum cytokine concentrations will be measured at the time of drug infusion of JNJ-64407564 for biomarker assessment.
Measure:Biomarker Assessment of JNJ-64007957
Time Frame:Up to Cycle 7 Day 1 (each cycle of 28-days)
Safety Issue:
Description:Serum cytokine concentrations will be measured at the time of drug infusion of JNJ-64007957 for biomarker assessment.
Measure:Number of Participants With Anti-Drug Antibodies to Daratumumab
Time Frame:Up to 40 Weeks
Safety Issue:
Description:Number of participants with anti-drug antibodies to daratumumab will be assessed.
Measure:Number of Participants With Anti-Drug Antibodies to JNJ-64407564
Time Frame:Up to 40 Weeks
Safety Issue:
Description:Number of participants with anti-drug antibodies to JNJ-64407564 will be assessed.
Measure:Number of Participants With Anti-Drug Antibodies to JNJ-64007957
Time Frame:Up to 40 Weeks
Safety Issue:
Description:Number of Participants with anti-drug antibodies to JNJ-64007957 will be assessed.
Measure:Overall Response Rate (ORR)
Time Frame:Up to 48 Weeks
Safety Issue:
Description: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.
Measure:Clinical Benefit Rate
Time Frame:Up to 48 Weeks
Safety Issue:
Description:Clinical benefit rate (ORR + minimal response [MR]) is defined as the of participants who have a MR or better according to the IMWG criteria.
Measure:Duration of Response (DOR)
Time Frame:Up to 48 Weeks
Safety Issue:
Description: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.
Measure:Time to Response
Time Frame:Up to 48 Weeks
Safety Issue:
Description: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.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Janssen Research & Development, LLC

Last Updated

December 5, 2019