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

Multiple Myeloma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03357952
• Other study ID #: CR108381
• Secondary ID: 2017-002611-3454
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: November 16, 2017
• Est. completion date: November 19, 2021

Study information

• Verified date: December 2022
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: November 19, 2021
• Est. primary completion date: October 24, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

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).
• 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.

Locations

Country	Name	City	State
Belgium	ZNA Stuivenberg	Antwerpen
Belgium	Algemeen Ziekenhuis Klina	Brasschaat
Belgium	AZ St.-Jan Brugge-Oostende AV	Brugge
Belgium	UZBrussel	Brussel
Belgium	UZA	Edegem
Belgium	UZ Gent	Gent
Belgium	Az Groeninge	Kortrijk
Israel	Carmel Hospital	Haifa
Israel	Rambam Medical Center	Haifa
Israel	Hadassah Medical Center	Jerusalem
Israel	Sourasky Medical Center	Tel-Aviv
Spain	Hosp. Univ. Germans Trias I Pujol	Badalona
Spain	Clinica Univ. de Navarra	Pamplona

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

Belgium,  Israel,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
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.	Up to 2 years
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.	Cycle 1 (28 days)
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.	Up to 2 years