Working…
Help guide our efforts to modernize ClinicalTrials.gov.
Send us your comments by March 14, 2020.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04108195
Recruitment Status : Not yet recruiting
First Posted : September 30, 2019
Last Update Posted : December 6, 2019
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Drug: Daratumumab Drug: JNJ-64407564 Drug: JNJ-64007957 Phase 1

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 100 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
Estimated Study Start Date : January 15, 2020
Estimated Primary Completion Date : January 14, 2021
Estimated Study Completion Date : April 14, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Multiple Myeloma
Drug Information available for: Daratumumab

Arm Intervention/treatment
Experimental: Part 1: Dose Escalation
Participants 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.
Drug: Daratumumab
Participants will receive daratumumab SC.
Other Name: JNJ-54767414, Darzalex

Drug: JNJ-64407564
Participants will receive JNJ-64407564 IV.
Other Name: Anti-GPRC5DxCD3

Drug: JNJ-64007957
Participants will receive JNJ-64007957 IV.
Other Name: Anti-BCMAxCD3

Experimental: Part 2: Dose Expansion
Participants 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.
Drug: Daratumumab
Participants will receive daratumumab SC.
Other Name: JNJ-54767414, Darzalex

Drug: JNJ-64407564
Participants will receive JNJ-64407564 IV.
Other Name: Anti-GPRC5DxCD3

Drug: JNJ-64007957
Participants will receive JNJ-64007957 IV.
Other Name: Anti-BCMAxCD3




Primary Outcome Measures :
  1. Part 1: Number of Participants With Dose Limiting Toxicity (DLT) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to 40 Weeks ]
    Serum concentration of daratumumab will be assessed.

  2. Serum Concentration of JNJ-64407564 [ Time Frame: Up to 40 Weeks ]
    Serum concentration of JNJ-64407564 will be assessed.

  3. Serum Concentration of JNJ-64007957 [ Time Frame: Up to 40 Weeks ]
    Serum concentration of JNJ-64007957 will be assessed.

  4. Biomarker Assessment of Daratumumab [ Time Frame: 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 JNJ-64407564 [ Time Frame: Up to Cycle 7 Day 1 (each cycle of 28-days) ]
    Serum cytokine concentrations will be measured at the time of drug infusion of JNJ-64407564 for biomarker assessment.

  6. Biomarker Assessment of JNJ-64007957 [ Time Frame: Up to Cycle 7 Day 1 (each cycle of 28-days) ]
    Serum cytokine concentrations will be measured at the time of drug infusion of JNJ-64007957 for biomarker assessment.

  7. Number of Participants With Anti-Drug Antibodies to Daratumumab [ Time Frame: 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 JNJ-64407564 [ Time Frame: Up to 40 Weeks ]
    Number of participants with anti-drug antibodies to JNJ-64407564 will be assessed.

  9. Number of Participants With Anti-Drug Antibodies to JNJ-64007957 [ Time Frame: Up to 40 Weeks ]
    Number of Participants with anti-drug antibodies to JNJ-64007957 will be assessed.

  10. Overall Response Rate (ORR) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04108195


Contacts
Layout table for location contacts
Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com

Locations
Show Show 17 study locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Layout table for investigator information
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC

Layout table for additonal information
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT04108195    
Other Study ID Numbers: CR108620
2019-000330-19 ( EudraCT Number )
64407564MMY1002 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: September 30, 2019    Key Record Dates
Last Update Posted: December 6, 2019
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
URL: https://www.janssen.com/clinical-trials/transparency

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Daratumumab
Antibodies
Antibodies, Monoclonal
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents