A Study of JNJ-63723283, an Anti-programmed Death-1 Monoclonal Antibody, Administered in Combination With Daratumumab, Compared With Daratumumab Alone in Participants With Relapsed or Refractory Multiple Myeloma

Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT03357952
Collaborator
(none)
10
Enrollment
13
Locations
2
Arms
48.1
Actual Duration (Months)
0.8
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The main purpose of this study is to assess the safety of the combination of JNJ-63723283 and daratumumab (Part 1); to compare the overall response rate (ORR) in participants treated with JNJ-63723283 in combination with daratumumab versus daratumumab alone (Part 2); and to compare progression-free survival (PFS) in participants treated with JNJ-63723283 in combination with daratumumab versus daratumumab alone (Part 3).

Condition or DiseaseIntervention/TreatmentPhase
Phase 2/Phase 3

Detailed Description

This is a multi-phase study of JNJ-63723283 in combination with daratumumab compared with daratumumab alone in participants with multiple myeloma who have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) or whose disease is double refractory to both a PI and an IMiD. The study consists of Screening Phase (procedures performed within 28 days before enrollment), Open-Label Treatment Phase (with End-of-Treatment Visit to occur 4 weeks after the last dose of study treatment) and Follow-up phase (8 weeks after the last dose of study treatment). Ongoing safety evaluation during Part 1 and Part 2 will be overseen by the Safety Evaluation Team (SET). In Part 3, ongoing safety and efficacy evaluation will be performed by the Independent Data Monitoring Committee (IDMC).

Study Design

Study Type:
Interventional
Actual Enrollment :
10 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized, Open-label, Multicenter, Multiphase Study of JNJ-63723283, an Anti-PD-1 Monoclonal Antibody, Administered in Combination With Daratumumab, Compared With Daratumumab Alone in Subjects With Relapsed or Refractory Multiple Myeloma
Actual Study Start Date :
Nov 16, 2017
Actual Primary Completion Date :
Oct 24, 2018
Actual Study Completion Date :
Nov 19, 2021

Arms and Interventions

ArmIntervention/Treatment
Experimental: Part 1: JNJ-63723283 + Daratumumab

Participants in Safety Run-in cohort will receive daratumumab IV and JNJ-63723283 IV for 1 cycle (28 days). Participants will continue to receive study treatment until confirmed disease progression, unacceptable toxicity, or any other treatment discontinuation criteria are met. Participants who were previously receiving JNJ-283 plus daratumumab have the opportunity to continue daratumumab therapy alone.

Drug: Daratumumab
Participants will receive daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) once every week for 8 weeks (Weeks 1 to 8); then once every other week for 16 weeks (Weeks 9 to 24); then once every 4 weeks (Week 25 onwards).
Other Names:
  • JNJ-54767414
  • Drug: JNJ-63723283
    Participants will receive JNJ-63723283 240 mg IV during Week 1 on Cycle 1 Day 2, Cycle 1 Day 15, then every 2 weeks thereafter.

    Experimental: Part 2 and Part 3: Daratumumab/ JNJ-63723283 + Daratumumab

    Participants in Treatment Arm A will receive daratumumab IV and in Treatment Arm B will receive daratumumab IV and JNJ-63723283 IV for cycles of 28 days each. All participants will continue to receive study treatment until confirmed disease progression, unacceptable toxicity, or any other treatment discontinuation criteria are met. Participants who were previously receiving JNJ-283 plus daratumumab have the opportunity to continue daratumumab therapy alone.

    Drug: Daratumumab
    Participants will receive daratumumab 16 milligram per kilogram (mg/kg) intravenously (IV) once every week for 8 weeks (Weeks 1 to 8); then once every other week for 16 weeks (Weeks 9 to 24); then once every 4 weeks (Week 25 onwards).
    Other Names:
  • JNJ-54767414
  • Drug: JNJ-63723283
    Participants will receive JNJ-63723283 240 mg IV during Week 1 on Cycle 1 Day 2, Cycle 1 Day 15, then every 2 weeks thereafter.

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Treatment Emergent Adverse Events (TEAE) in Safety run-in Phase (Part 1) [Up to 2 years]

      An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs are adverse events (AEs) which will occur up to 2 years that were absent before treatment or that worsened relative to pre-treatment state.

    2. Number of Participants With Dose Limiting Toxicity in Safety run-in Phase (Part 1) [Cycle 1 (28 days)]

      Dose limiting toxicity defined as an adverse event or adverse drug reaction experienced by the participants during observation of 28 days (Part 1) of treatment Cycle 1.

    Secondary Outcome Measures

    1. Number of Participants With Treatment Emergent Adverse Events (TEAE) in Part 2 [Up to 2 years]

      An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs are adverse events (AEs) which will occur up to 2 years that were absent before treatment or that worsened relative to pre-treatment state.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Have received at least 3 prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD) in any order during the course of treatment for multiple myeloma or have disease that is refractory to both a PI and an IMiD

    • Evidence of a response (partial response [PR] or better based on investigator's determination of response by International Myeloma Working Group [IMWG] criteria) to at least 1 prior treatment regimen

    • Documented measurable disease for multiple myeloma at screening as defined in protocol

    • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2

    • Contraceptive use by men or women should be consistent with local regulations regarding the use of contraceptive methods for participants participating in clinical studies

    Exclusion Criteria:
    • Received any of the following prescribed medications or therapies in the past: Anti-CD38 antibody, including daratumumab, and/or Anti-PD-1 (programmed death-1) and anti-PD-L1 (programmed death-ligand 1) antibodies

    • Plans to undergo a stem cell transplant prior to progression of disease on this study (these participants should not be enrolled to reduce disease burden prior to transplant)

    • History of malignancy (other than multiple myeloma) within 2 years prior to first administration of study drug (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy that in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 3 years)

    • Clinical signs of meningeal involvement of multiple myeloma

    • Known chronic obstructive pulmonary disease (COPD) with a forced expiratory volume in 1 second (FEV1) <50% of predicted normal or known moderate or severe persistent asthma within the past 2 years, or uncontrolled asthma of any classification

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1ZNA StuivenbergAntwerpenBelgium2060
    2Algemeen Ziekenhuis KlinaBrasschaatBelgium2930
    3AZ St.-Jan Brugge-Oostende AVBruggeBelgium8000
    4UZBrusselBrusselBelgium1090
    5UZAEdegemBelgium2650
    6UZ GentGentBelgium9000
    7Az GroeningeKortrijkBelgium8500
    8Rambam Medical CenterHaifaIsrael31096
    9Carmel HospitalHaifaIsrael34362
    10Hadassah Medical CenterJerusalemIsrael91120
    11Sourasky Medical CenterTel-AvivIsrael6423906
    12Hosp. Univ. Germans Trias I PujolBadalonaSpain08916
    13Clinica Univ. de NavarraPamplonaSpain31008

    Sponsors and Collaborators

    • Janssen Research & Development, LLC

    Investigators

    • Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Janssen Research & Development, LLC
    ClinicalTrials.gov Identifier:
    NCT03357952
    Other Study ID Numbers:
    • CR108381
    • 2017-002611-34
    • 54767414MMY2036
    First Posted:
    Nov 30, 2017
    Last Update Posted:
    Jan 12, 2022
    Last Verified:
    Dec 1, 2021
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    Yes
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment DetailA total of 10 participants were enrolled in the study. Among these, 9 participants were included in the Safety Run-in phase (Part 1) who received daratumumab intravenous (IV) and JNJ-63723283 IV and 1 participant randomized to Arm A in Part 2 of the study who received daratumumab IV alone.
    Arm/Group TitlePart 1: Daratumumab + JNJ-63723283Part 2: Daratumumab (Arm A)
    Arm/Group DescriptionParticipants in Safety Run-in cohort received daratumumab 16 mg/kg IV once every week (Weeks 1 to 8); then once every other week for 16 weeks (Weeks 9 to 24); then once every 4 weeks (Week 25 onwards) and JNJ-63723283 240 mg IV during Week 1 on Cycle 1 Day 2, Cycle 1 Day 15, then every 2 weeks thereafter. Each treatment cycle consisted of 28 days. Participants continued to receive study treatment until confirmed disease progression, unacceptable toxicity, or any other treatment discontinuation criteria were met.Participants in treatment Arm A received daratumumab 16 mg/kg IV once every week (Weeks 1 to 8); then once every other week for 16 weeks (Weeks 9 to 24); then once every 4 weeks (Week 25 onwards). All participants were continued to receive study treatment until confirmed disease progression, unacceptable toxicity, or any other treatment discontinuation criteria were met.
    Period Title: Overall Study
    STARTED91
    COMPLETED00
    NOT COMPLETED91

    Baseline Characteristics

    Arm/Group TitlePart 1: Daratumumab + JNJ-63723283Part 2: Daratumumab (Arm A)Total
    Arm/Group DescriptionParticipants in Safety Run-in cohort received daratumumab 16 mg/kg IV once every week (Weeks 1 to 8); then once every other week for 16 weeks (Weeks 9 to 24); then once every 4 weeks (Week 25 onwards) and JNJ-63723283 240 mg IV during Week 1 on Cycle 1 Day 2, Cycle 1 Day 15, then every 2 weeks thereafter. Each treatment cycle consisted of 28 days. Participants continued to receive study treatment until confirmed disease progression, unacceptable toxicity, or any other treatment discontinuation criteria were met.Participants in treatment Arm A received daratumumab 16 mg/kg IV once every week (Weeks 1 to 8); then once every other week for 16 weeks (Weeks 9 to 24); then once every 4 weeks (Week 25 onwards). All participants were continued to receive study treatment until confirmed disease progression, unacceptable toxicity, or any other treatment discontinuation criteria were met.Total of all reporting groups
    Overall Participants9110
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    63
    (10.97)
    43
    61
    (12.12)
    Sex: Female, Male (Count of Participants)
    Female
    4
    44.4%
    0
    0%
    4
    40%
    Male
    5
    55.6%
    1
    100%
    6
    60%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    0
    0%
    0
    0%
    0
    0%
    Not Hispanic or Latino
    9
    100%
    1
    100%
    10
    100%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    1
    11.1%
    0
    0%
    1
    10%
    White
    8
    88.9%
    1
    100%
    9
    90%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    0
    0%
    Region of Enrollment (Count of Participants)
    Belgium
    4
    44.4%
    0
    0%
    4
    40%
    Israel
    4
    44.4%
    1
    100%
    5
    50%
    Spain
    1
    11.1%
    0
    0%
    1
    10%

    Outcome Measures

    1. Primary Outcome
    TitleNumber of Participants With Treatment Emergent Adverse Events (TEAE) in Safety run-in Phase (Part 1)
    DescriptionAn adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs are adverse events (AEs) which will occur up to 2 years that were absent before treatment or that worsened relative to pre-treatment state.
    Time FrameUp to 2 years

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all participants who have received at least 1 dose of study agent (JNJ-63723283 or daratumumab, partial or complete) in safety run-in phase of the study.
    Arm/Group TitlePart 1: Daratumumab + JNJ-63723283
    Arm/Group DescriptionParticipants in Safety Run-in cohort received daratumumab 16 mg/kg IV once every week (Weeks 1 to 8); then once every other week for 16 weeks (Weeks 9 to 24); then once every 4 weeks (Week 25 onwards) and JNJ-63723283 240 mg IV during Week 1 on Cycle 1 Day 2, Cycle 1 Day 15, then every 2 weeks thereafter. Each treatment cycle consisted of 28 days. Participants continued to receive study treatment until confirmed disease progression, unacceptable toxicity, or any other treatment discontinuation criteria were met.
    Measure Participants9
    Count of Participants [Participants]
    9
    100%
    2. Primary Outcome
    TitleNumber of Participants With Dose Limiting Toxicity in Safety run-in Phase (Part 1)
    DescriptionDose limiting toxicity defined as an adverse event or adverse drug reaction experienced by the participants during observation of 28 days (Part 1) of treatment Cycle 1.
    Time FrameCycle 1 (28 days)

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all participants who have received at least 1 dose of study agent (JNJ-63723283 or daratumumab, partial or complete) in safety run-in phase.
    Arm/Group TitlePart 1: Daratumumab + JNJ-63723283
    Arm/Group DescriptionParticipants in Safety Run-in cohort received daratumumab 16 mg/kg IV once every week (Weeks 1 to 8); then once every other week for 16 weeks (Weeks 9 to 24); then once every 4 weeks (Week 25 onwards) and JNJ-63723283 240 mg IV during Week 1 on Cycle 1 Day 2, Cycle 1 Day 15, then every 2 weeks thereafter. Each treatment cycle consisted of 28 days. Participants continued to receive study treatment until confirmed disease progression, unacceptable toxicity, or any other treatment discontinuation criteria were met.
    Measure Participants9
    Count of Participants [Participants]
    0
    0%
    3. Secondary Outcome
    TitleNumber of Participants With Treatment Emergent Adverse Events (TEAE) in Part 2
    DescriptionAn adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs are adverse events (AEs) which will occur up to 2 years that were absent before treatment or that worsened relative to pre-treatment state.
    Time FrameUp to 2 years

    Outcome Measure Data

    Analysis Population Description
    Safety analysis set included all participants who have received at least 1 dose of study agent in Part 2 of the study.
    Arm/Group TitlePart 2: Daratumumab (Arm A)
    Arm/Group DescriptionParticipants in treatment Arm A received daratumumab 16 mg/kg IV once every week (Weeks 1 to 8); then once every other week for 16 weeks (Weeks 9 to 24); then once every 4 weeks (Week 25 onwards). All participants were continued to receive study treatment until confirmed disease progression, unacceptable toxicity, or any other treatment discontinuation criteria were met.
    Measure Participants1
    Count of Participants [Participants]
    1
    11.1%

    Adverse Events

    Time FrameUp to 2 years
    Adverse Event Reporting Description
    Arm/Group TitlePart 1: Daratumumab + JNJ-63723283Part 2: Daratumumab (Arm A)
    Arm/Group DescriptionParticipants in Safety Run-in cohort received daratumumab 16 mg/kg IV once every week (Weeks 1 to 8); then once every other week for 16 weeks (Weeks 9 to 24); then once every 4 weeks (Week 25 onwards) and JNJ-63723283 240 mg IV during Week 1 on Cycle 1 Day 2, Cycle 1 Day 15, then every 2 weeks thereafter. Each treatment cycle consisted of 28 days. Participants continued to receive study treatment until confirmed disease progression, unacceptable toxicity, or any other treatment discontinuation criteria were met.Participants in treatment Arm A received daratumumab 16 mg/kg IV once every week (Weeks 1 to 8); then once every other week for 16 weeks (Weeks 9 to 24); then once every 4 weeks (Week 25 onwards). All participants were continued to receive study treatment until confirmed disease progression, unacceptable toxicity, or any other treatment discontinuation criteria were met.
    All Cause Mortality
    Part 1: Daratumumab + JNJ-63723283Part 2: Daratumumab (Arm A)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total0/9 (0%) 0/1 (0%)
    Serious Adverse Events
    Part 1: Daratumumab + JNJ-63723283Part 2: Daratumumab (Arm A)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total3/9 (33.3%) 0/1 (0%)
    Blood and lymphatic system disorders
    Febrile Neutropenia1/9 (11.1%) 0/1 (0%)
    Infections and infestations
    Septic Shock1/9 (11.1%) 0/1 (0%)
    Nervous system disorders
    Encephalitis Autoimmune1/9 (11.1%) 0/1 (0%)
    Renal and urinary disorders
    Acute Kidney Injury1/9 (11.1%) 0/1 (0%)
    Other (Not Including Serious) Adverse Events
    Part 1: Daratumumab + JNJ-63723283Part 2: Daratumumab (Arm A)
    Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
    Total9/9 (100%) 1/1 (100%)
    Blood and lymphatic system disorders
    Anaemia3/9 (33.3%) 0/1 (0%)
    Leukopenia1/9 (11.1%) 0/1 (0%)
    Lymphopenia2/9 (22.2%) 0/1 (0%)
    Neutropenia4/9 (44.4%) 0/1 (0%)
    Thrombocytopenia3/9 (33.3%) 1/1 (100%)
    Cardiac disorders
    Bradycardia1/9 (11.1%) 0/1 (0%)
    Ear and labyrinth disorders
    Vertigo1/9 (11.1%) 0/1 (0%)
    Eye disorders
    Corneal Degeneration1/9 (11.1%) 0/1 (0%)
    Gastrointestinal disorders
    Constipation1/9 (11.1%) 0/1 (0%)
    Diarrhoea2/9 (22.2%) 0/1 (0%)
    Dry Mouth1/9 (11.1%) 0/1 (0%)
    Dyspepsia1/9 (11.1%) 0/1 (0%)
    Nausea3/9 (33.3%) 0/1 (0%)
    Vomiting3/9 (33.3%) 0/1 (0%)
    General disorders
    Asthenia2/9 (22.2%) 0/1 (0%)
    Chills2/9 (22.2%) 0/1 (0%)
    Fatigue3/9 (33.3%) 0/1 (0%)
    Influenza Like Illness1/9 (11.1%) 0/1 (0%)
    Oedema Peripheral1/9 (11.1%) 0/1 (0%)
    Pyrexia1/9 (11.1%) 0/1 (0%)
    Infections and infestations
    Body Tinea1/9 (11.1%) 0/1 (0%)
    Cellulitis1/9 (11.1%) 0/1 (0%)
    Herpes Simplex1/9 (11.1%) 0/1 (0%)
    Osteomyelitis1/9 (11.1%) 0/1 (0%)
    Rhinitis1/9 (11.1%) 0/1 (0%)
    Upper Respiratory Tract Infection1/9 (11.1%) 0/1 (0%)
    Viral Upper Respiratory Tract Infection1/9 (11.1%) 0/1 (0%)
    Vulvovaginal Candidiasis1/9 (11.1%) 0/1 (0%)
    Investigations
    Lipase Increased1/9 (11.1%) 0/1 (0%)
    Weight Decreased1/9 (11.1%) 0/1 (0%)
    Metabolism and nutrition disorders
    Dehydration1/9 (11.1%) 0/1 (0%)
    Folate Deficiency1/9 (11.1%) 0/1 (0%)
    Hyperamylasaemia1/9 (11.1%) 0/1 (0%)
    Hyperglycaemia1/9 (11.1%) 0/1 (0%)
    Hypomagnesaemia1/9 (11.1%) 0/1 (0%)
    Musculoskeletal and connective tissue disorders
    Back Pain1/9 (11.1%) 0/1 (0%)
    Muscle Atrophy1/9 (11.1%) 0/1 (0%)
    Muscle Spasms1/9 (11.1%) 0/1 (0%)
    Musculoskeletal Pain1/9 (11.1%) 0/1 (0%)
    Myalgia3/9 (33.3%) 0/1 (0%)
    Myopathy1/9 (11.1%) 0/1 (0%)
    Nervous system disorders
    Dizziness1/9 (11.1%) 0/1 (0%)
    Paraesthesia2/9 (22.2%) 0/1 (0%)
    Renal and urinary disorders
    Proteinuria1/9 (11.1%) 0/1 (0%)
    Respiratory, thoracic and mediastinal disorders
    Cough2/9 (22.2%) 0/1 (0%)
    Dysphonia1/9 (11.1%) 0/1 (0%)
    Dyspnoea1/9 (11.1%) 0/1 (0%)
    Epistaxis1/9 (11.1%) 0/1 (0%)
    Rhinitis Allergic1/9 (11.1%) 0/1 (0%)
    Throat Irritation1/9 (11.1%) 0/1 (0%)
    Skin and subcutaneous tissue disorders
    Pruritus1/9 (11.1%) 0/1 (0%)
    Vascular disorders
    Hypertension2/9 (22.2%) 0/1 (0%)

    Limitations/Caveats

    Single participant enrolled in Part 2 was not evaluable for efficacy, hence data for Part 2 efficacy outcome measures was not collected. Sponsor suspended enrollment during Part 2, hence Part 2 stopped early, and Part 3 was not conducted.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.

    Results Point of Contact

    Name/TitleExecutive Medical Director
    OrganizationJanssen Research & Development, LLC
    Phone844-434-4210
    EmailClinicalTrialDisclosure@its.jnj.com
    Responsible Party:
    Janssen Research & Development, LLC
    ClinicalTrials.gov Identifier:
    NCT03357952
    Other Study ID Numbers:
    • CR108381
    • 2017-002611-34
    • 54767414MMY2036
    First Posted:
    Nov 30, 2017
    Last Update Posted:
    Jan 12, 2022
    Last Verified:
    Dec 1, 2021