Multiple Myeloma
Conditions
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).
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).
Interventions
DRUGDaratumumab
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).
DRUGJNJ-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.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Belgium, Israel, Spain
Participant flow
Pre-assignment details
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.
Participants by arm
| Arm | Count |
|---|---|
| Part 1: Daratumumab + JNJ-63723283 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. | 9 |
| Part 2: Daratumumab (Arm A) 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. | 1 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Sponsor Decision | 9 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Part 1: Daratumumab + JNJ-63723283 | Part 2: Daratumumab (Arm A) | Total |
|---|---|---|---|
| Age, Continuous | 63 years STANDARD_DEVIATION 10.97 | 43 years | 61 years STANDARD_DEVIATION 12.12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 9 Participants | 1 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 1 Participants | 9 Participants |
| Region of Enrollment Belgium | 4 Participants | 0 Participants | 4 Participants |
| Region of Enrollment Israel | 4 Participants | 1 Participants | 5 Participants |
| Region of Enrollment Spain | 1 Participants | 0 Participants | 1 Participants |
| Sex: Female, Male Female | 4 Participants | 0 Participants | 4 Participants |
| Sex: Female, Male Male | 5 Participants | 1 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 1 |
| other Total, other adverse events | 9 / 9 | 1 / 1 |
| serious Total, serious adverse events | 3 / 9 | 0 / 1 |
Outcome results
Primary
Number of Participants With Dose Limiting Toxicity in Safety run-in Phase (Part 1)
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)
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Daratumumab + JNJ-63723283 | Number of Participants With Dose Limiting Toxicity in Safety run-in Phase (Part 1) | 0 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAE) in Safety run-in Phase (Part 1)
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
Population: 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 | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Daratumumab + JNJ-63723283 | Number of Participants With Treatment Emergent Adverse Events (TEAE) in Safety run-in Phase (Part 1) | 9 Participants |
Secondary
Number of Participants With Treatment Emergent Adverse Events (TEAE) in Part 2
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
Population: Safety analysis set included all participants who have received at least 1 dose of study agent in Part 2 of the study.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1: Daratumumab + JNJ-63723283 | Number of Participants With Treatment Emergent Adverse Events (TEAE) in Part 2 | 1 Participants |