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

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

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).

Study Overview

• Status: Completed
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Daratumumab; Drug: JNJ-63723283

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 Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Antwerpen, Belgium, 2060
    • ZNA Stuivenberg
  • Brasschaat, Belgium, 2930
    • Algemeen Ziekenhuis Klina
  • Brugge, Belgium, 8000
    • AZ St.-Jan Brugge-Oostende AV
  • Brussel, Belgium, 1090
    • UZBrussel
  • Edegem, Belgium, 2650
    • UZA
  • Gent, Belgium, 9000
    • UZ Gent
  • Kortrijk, Belgium, 8500
    • Az Groeninge
• Israel
  • Haifa, Israel, 31096
    • Rambam Medical Center
  • Haifa, Israel, 34362
    • Carmel Hospital
  • Jerusalem, Israel, 91120
    • Hadassah Medical Center
  • Tel-Aviv, Israel, 6423906
    • Sourasky Medical Center
• Spain
  • Badalona, Spain, 08916
    • Hosp. Univ. Germans Trias I Pujol
  • Pamplona, Spain, 31008
    • Clinica Univ. de Navarra

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 2 years
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.	Cycle 1 (28 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Up to 2 years

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): November 16, 2017
• Primary Completion (Actual): October 24, 2018
• Study Completion (Actual): November 19, 2021

Study Registration Dates

• First Submitted: November 13, 2017
• First Submitted That Met QC Criteria: November 29, 2017
• First Posted (Actual): November 30, 2017

Study Record Updates

• Last Update Posted (Actual): December 5, 2022
• Last Update Submitted That Met QC Criteria: December 1, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Antineoplastic Agents; Daratumumab
• Other Study ID Numbers: CR108381; 2017-002611-34 (EudraCT Number); 54767414MMY2036 (Other Identifier: Janssen Research & Development, LLC)

Drug and device information, study documents

• 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