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
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 Disease | Intervention/Treatment | Phase |
---|---|---|
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
Arms and Interventions
Arm | Intervention/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:
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:
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
- 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.
- 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
- 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
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
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | ZNA Stuivenberg | Antwerpen | Belgium | 2060 | |
2 | Algemeen Ziekenhuis Klina | Brasschaat | Belgium | 2930 | |
3 | AZ St.-Jan Brugge-Oostende AV | Brugge | Belgium | 8000 | |
4 | UZBrussel | Brussel | Belgium | 1090 | |
5 | UZA | Edegem | Belgium | 2650 | |
6 | UZ Gent | Gent | Belgium | 9000 | |
7 | Az Groeninge | Kortrijk | Belgium | 8500 | |
8 | Rambam Medical Center | Haifa | Israel | 31096 | |
9 | Carmel Hospital | Haifa | Israel | 34362 | |
10 | Hadassah Medical Center | Jerusalem | Israel | 91120 | |
11 | Sourasky Medical Center | Tel-Aviv | Israel | 6423906 | |
12 | Hosp. Univ. Germans Trias I Pujol | Badalona | Spain | 08916 | |
13 | Clinica Univ. de Navarra | Pamplona | Spain | 31008 |
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.- CR108381
- 2017-002611-34
- 54767414MMY2036
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail | A 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 Title | Part 1: Daratumumab + JNJ-63723283 | Part 2: Daratumumab (Arm A) |
---|---|---|
Arm/Group Description | Participants 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 | ||
STARTED | 9 | 1 |
COMPLETED | 0 | 0 |
NOT COMPLETED | 9 | 1 |
Baseline Characteristics
Arm/Group Title | Part 1: Daratumumab + JNJ-63723283 | Part 2: Daratumumab (Arm A) | Total |
---|---|---|---|
Arm/Group Description | Participants 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 Participants | 9 | 1 | 10 |
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
Title | Number of Participants With Treatment Emergent Adverse Events (TEAE) in Safety run-in Phase (Part 1) |
---|---|
Description | 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. |
Time Frame | Up 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 Title | Part 1: Daratumumab + JNJ-63723283 |
---|---|
Arm/Group Description | Participants 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 Participants | 9 |
Count of Participants [Participants] |
9
100%
|
Title | Number of Participants With Dose Limiting Toxicity in Safety run-in Phase (Part 1) |
---|---|
Description | 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. |
Time Frame | Cycle 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 Title | Part 1: Daratumumab + JNJ-63723283 |
---|---|
Arm/Group Description | Participants 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 Participants | 9 |
Count of Participants [Participants] |
0
0%
|
Title | Number of Participants With Treatment Emergent Adverse Events (TEAE) in Part 2 |
---|---|
Description | 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. |
Time Frame | Up 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 Title | Part 2: Daratumumab (Arm A) |
---|---|
Arm/Group Description | 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. |
Measure Participants | 1 |
Count of Participants [Participants] |
1
11.1%
|
Adverse Events
Time Frame | Up to 2 years | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | Part 1: Daratumumab + JNJ-63723283 | Part 2: Daratumumab (Arm A) | ||
Arm/Group Description | Participants 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-63723283 | Part 2: Daratumumab (Arm A) | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/9 (0%) | 0/1 (0%) | ||
Serious Adverse Events |
||||
Part 1: Daratumumab + JNJ-63723283 | Part 2: Daratumumab (Arm A) | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 3/9 (33.3%) | 0/1 (0%) | ||
Blood and lymphatic system disorders | ||||
Febrile Neutropenia | 1/9 (11.1%) | 0/1 (0%) | ||
Infections and infestations | ||||
Septic Shock | 1/9 (11.1%) | 0/1 (0%) | ||
Nervous system disorders | ||||
Encephalitis Autoimmune | 1/9 (11.1%) | 0/1 (0%) | ||
Renal and urinary disorders | ||||
Acute Kidney Injury | 1/9 (11.1%) | 0/1 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
Part 1: Daratumumab + JNJ-63723283 | Part 2: Daratumumab (Arm A) | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 9/9 (100%) | 1/1 (100%) | ||
Blood and lymphatic system disorders | ||||
Anaemia | 3/9 (33.3%) | 0/1 (0%) | ||
Leukopenia | 1/9 (11.1%) | 0/1 (0%) | ||
Lymphopenia | 2/9 (22.2%) | 0/1 (0%) | ||
Neutropenia | 4/9 (44.4%) | 0/1 (0%) | ||
Thrombocytopenia | 3/9 (33.3%) | 1/1 (100%) | ||
Cardiac disorders | ||||
Bradycardia | 1/9 (11.1%) | 0/1 (0%) | ||
Ear and labyrinth disorders | ||||
Vertigo | 1/9 (11.1%) | 0/1 (0%) | ||
Eye disorders | ||||
Corneal Degeneration | 1/9 (11.1%) | 0/1 (0%) | ||
Gastrointestinal disorders | ||||
Constipation | 1/9 (11.1%) | 0/1 (0%) | ||
Diarrhoea | 2/9 (22.2%) | 0/1 (0%) | ||
Dry Mouth | 1/9 (11.1%) | 0/1 (0%) | ||
Dyspepsia | 1/9 (11.1%) | 0/1 (0%) | ||
Nausea | 3/9 (33.3%) | 0/1 (0%) | ||
Vomiting | 3/9 (33.3%) | 0/1 (0%) | ||
General disorders | ||||
Asthenia | 2/9 (22.2%) | 0/1 (0%) | ||
Chills | 2/9 (22.2%) | 0/1 (0%) | ||
Fatigue | 3/9 (33.3%) | 0/1 (0%) | ||
Influenza Like Illness | 1/9 (11.1%) | 0/1 (0%) | ||
Oedema Peripheral | 1/9 (11.1%) | 0/1 (0%) | ||
Pyrexia | 1/9 (11.1%) | 0/1 (0%) | ||
Infections and infestations | ||||
Body Tinea | 1/9 (11.1%) | 0/1 (0%) | ||
Cellulitis | 1/9 (11.1%) | 0/1 (0%) | ||
Herpes Simplex | 1/9 (11.1%) | 0/1 (0%) | ||
Osteomyelitis | 1/9 (11.1%) | 0/1 (0%) | ||
Rhinitis | 1/9 (11.1%) | 0/1 (0%) | ||
Upper Respiratory Tract Infection | 1/9 (11.1%) | 0/1 (0%) | ||
Viral Upper Respiratory Tract Infection | 1/9 (11.1%) | 0/1 (0%) | ||
Vulvovaginal Candidiasis | 1/9 (11.1%) | 0/1 (0%) | ||
Investigations | ||||
Lipase Increased | 1/9 (11.1%) | 0/1 (0%) | ||
Weight Decreased | 1/9 (11.1%) | 0/1 (0%) | ||
Metabolism and nutrition disorders | ||||
Dehydration | 1/9 (11.1%) | 0/1 (0%) | ||
Folate Deficiency | 1/9 (11.1%) | 0/1 (0%) | ||
Hyperamylasaemia | 1/9 (11.1%) | 0/1 (0%) | ||
Hyperglycaemia | 1/9 (11.1%) | 0/1 (0%) | ||
Hypomagnesaemia | 1/9 (11.1%) | 0/1 (0%) | ||
Musculoskeletal and connective tissue disorders | ||||
Back Pain | 1/9 (11.1%) | 0/1 (0%) | ||
Muscle Atrophy | 1/9 (11.1%) | 0/1 (0%) | ||
Muscle Spasms | 1/9 (11.1%) | 0/1 (0%) | ||
Musculoskeletal Pain | 1/9 (11.1%) | 0/1 (0%) | ||
Myalgia | 3/9 (33.3%) | 0/1 (0%) | ||
Myopathy | 1/9 (11.1%) | 0/1 (0%) | ||
Nervous system disorders | ||||
Dizziness | 1/9 (11.1%) | 0/1 (0%) | ||
Paraesthesia | 2/9 (22.2%) | 0/1 (0%) | ||
Renal and urinary disorders | ||||
Proteinuria | 1/9 (11.1%) | 0/1 (0%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Cough | 2/9 (22.2%) | 0/1 (0%) | ||
Dysphonia | 1/9 (11.1%) | 0/1 (0%) | ||
Dyspnoea | 1/9 (11.1%) | 0/1 (0%) | ||
Epistaxis | 1/9 (11.1%) | 0/1 (0%) | ||
Rhinitis Allergic | 1/9 (11.1%) | 0/1 (0%) | ||
Throat Irritation | 1/9 (11.1%) | 0/1 (0%) | ||
Skin and subcutaneous tissue disorders | ||||
Pruritus | 1/9 (11.1%) | 0/1 (0%) | ||
Vascular disorders | ||||
Hypertension | 2/9 (22.2%) | 0/1 (0%) |
Limitations/Caveats
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/Title | Executive Medical Director |
---|---|
Organization | Janssen Research & Development, LLC |
Phone | 844-434-4210 |
ClinicalTrialDisclosure@its.jnj.com |
- CR108381
- 2017-002611-34
- 54767414MMY2036