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)
• Enrollment: 10
• Locations: 13
• Arms: 2
• Actual Duration (Months): 48.1
• Patients Per Site: 0.8
• Patients Per Site Per Month: 0

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
Multiple Myeloma	Drug: Daratumumab; Drug: JNJ-63723283	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

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: 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

	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)

• Study Protocol - Jun 20, 2018
• Statistical Analysis Plan - Sep 25, 2018

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: Multiple Myeloma; Neoplasms, Plasma Cell; Daratumumab

Study Results

Participant Flow

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

1. Primary Outcome

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%

2. Primary Outcome

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%

3. Secondary Outcome

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
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

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.