A Study of JNJ-67856633 in Participants With Non-Hodgkin's Lymphoma (NHL) and Chronic Lymphocytic Leukemia (CLL)

A Phase 1, First-in-Human, Open-Label Study of the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-67856633, an Inhibitor of MALT1, in Participants With NHL and CLL

The purpose of this study is to determine the recommended Phase 2 dose regimen or the maximum tolerated dose of JNJ-67856633 in participants with relapsed/ refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia.

Study Overview

• Status: Active, not recruiting
• Conditions: Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell
• Intervention / Treatment: Drug: JNJ-67856633

Detailed Description

Non-Hodgkin lymphoma (NHL) represents a diverse set of diseases. Among them diffuse large B-cell lymphoma (DLBCL) represents the most common subtype of NHL, accounting for 30 percent (%) to 40% of all newly diagnosed cases. Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a key mediator of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) signaling pathway and has been shown to play a critical role in different types of lymphoma, including activated B cell-like (ABC) subtype of diffuse large B-cell lymphoma (DLBCL). JNJ-67856633 is a MALT1 inhibitor and will be administered orally. The study will evaluate the following: Dose Escalation (Part 1): One or more recommended Phase 2 dose (RP2Ds) of JNJ-67856633. Cohort Expansion (Part 2): JNJ-67856633 is well tolerated and achieves antitumor responses at the RP2D. The study consists of screening phase (less than or equal to 28 days before first dose), treatment phase (from Cycle 1 Day 1 till end of treatment visit [within 30 (+7) days after the last dose]) and post-treatment phase. A prescreening period may also apply to participants in select cohorts in Part 2. The total study duration will be approximately 4 years and 11 months. Efficacy assessments will include radiographic image assessments, positron emission tomography scan, bone marrow assessment, endoscopy or colonoscopy etc. Safety will be monitored throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 226
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Clayton, Australia, 3168
    • Monash Medical Centre
  • Melbourne, Australia, 3000
    • Peter MacCallum Cancer Centre
  • Nedlands, Australia, 6009
    • Linear Clinical Research Ltd
  • Randwick, Australia, 2031
    • Scientia Clinical Research
• China
  • Nanchang, China, 330006
    • The first affiliated Hospital of Nanchang University
  • Tianjin, China, 300060
    • Tianjin Medical University Cancer Institute and Hospital
  • Tianjin, China, 300320
    • Institute of Hematology & Blood Disease Hospital Chinese Academy of Medical Science
  • Xi'an, China
    • The First Affiliated Hospital of Xian Jiaotong University
• France
  • Lille, France, 59037
    • Hôpital Claude Huriez
  • Nantes Cedex 1, France, 44093
    • CHU de NANTES Hotel Dieu
  • PARIS Cedex 5, France, 75248
    • Institut Curie
  • Paris, France, 75013
    • Groupe Hospitalier Pitié Salpêtrière
  • Pierre Benite, France, 69495
    • Centre Hospitalier Lyon-Sud
  • Toulouse, France, 31059
    • Institut Universitaire Du Cancer Toulouse - Oncopole
  • Tours Cedex 9, France, 37044
    • CHU Bretonneau
  • VILLEJUIF Cedex, France, 94805
    • Institut Gustave Roussy
• Germany
  • Münster, Germany, 48149
    • Universitatsklinikum Munster
  • Ulm, Germany, 89081
    • Universitätsklinikum Ulm
• Greece
  • Athens, Greece, 11528
    • Alexandra General Hospital of Athens
• Israel
  • Jerusalem, Israel, 91120
    • Hadassah Medical Center
  • Ramat Gan, Israel, 74047
    • Sheba Medical Center
  • Tel Aviv, Israel, 64239
    • Tel Aviv Sourasky Medical Center
• Italy
  • Bologna, Italy, 40138
    • Azienda Opedaliero-Universitaria Policlinico Sant'orsola Malpighi di Bologna
  • Milano, Italy, 20162
    • Asst Grande Ospedale Metropolitano Niguarda
• Japan
  • Chuo-Ku, Japan, 104-0045
    • National Cancer Center Hospital
  • Isehara, Japan, 259-1193
    • Tokai University Hospital
  • Nagoya-shi, Japan, 460-0001
    • National Hospital Organization Nagoya Medical Center
  • Okayama, Japan, 700-8558
    • Okayama University Hospital
  • Tokyo, Japan, 135 8550
    • The Cancer Institute Hospital of Jfcr
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 06351
    • Samsung Medical Center
• Spain
  • Badalona, Barcelona, Spain, 8916
    • Hosp. Univ. Germans Trias I Pujol
  • Barcelona, Spain, 08035
    • Hospital de Vall D'Hebron
  • Madrid, Spain, 28040
    • Hosp. Univ. Fund. Jimenez Diaz
  • Madrid, Spain, 28041
    • Hosp. Univ. 12 de Octubre
  • Pamplona, Spain, 31008
    • Clinica Univ. de Navarra
  • Pozuelo de Alarcon, Spain, 28223
    • Hosp. Quiron Madrid Pozuelo
  • Salamanca, Spain, 37007
    • Hosp. Clinico Univ. de Salamanca
  • Santander, Spain, 39008
    • Hosp. Univ. Marques de Valdecilla
• United Kingdom
  • London, United Kingdom, EC1A 7BE
    • St Bartholomew'S Hospital
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Nebraska
    • Omaha, Nebraska, United States, 68198
      • University of Nebraska Medical Center
  • New York
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10029
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10021
      • Weill Cornell Medicine
  • Texas
    • Houston, Texas, United States, 77025
      • MD Anderson

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
• Cardiac parameters within the following range: corrected QT interval (QTc intervals corrected using Fridericia's formula [QTcF]) less than or equal to (<=)480 milliseconds based on the average of triplicate assessments performed no more than 5 minutes apart (plus minus [+-]3 minutes)
• Women of childbearing potential must have a negative highly sensitive serum (Beta human chorionic gonadotropin) at screening and prior to the first dose of study drug, and until 30 days after the last dose
• In addition to the user-independent, highly effective method of contraception, a male or female condom with or without spermicide is required, example, condom with spermicidal foam/gel/film/cream/suppository. Male condom and female condom should not be used together (due to risk of failure with friction)
• Men must wear a condom when engaging in any activity that allows for passage of ejaculate to another person. Male participants should also be advised of the benefit for a female partner to use a highly effective method of contraception as condom may break or leak

Exclusion Criteria:

• Known active central nervous system (CNS) involvement for dose escalation and specific expansion cohorts as determined by the study evaluation team (SET)
• Prior solid-organ transplantation
• Either of the following: a) Received an autologous stem cell transplant less than or equal to (<=)3 months before the first dose of study drug. b) Prior treatment with allogenic stem cell transplant <=6 months before the first dose of study drug, has evidence of graft versus host disease, or requires immunosuppressant therapy for graft versus host disease within the last 4 weeks
• History of malignancy (other than the disease under study in the cohort to which the participant is assigned) within 1 year prior to the first administration of study drug. Exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy which in the opinion of the investigator, with concurrence with the sponsor's medical monitor, is considered cured with minimal risk of recurrence within 1 year before the first dose of study drug. Concomitant malignancies that are unlikely to progress and/or preclude evaluation of study endpoints may be allowed after discussion with the Study Responsible Physician
• Prior treatment with a mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) inhibitor

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1 (Dose Escalation): JNJ-67856633; Participants will receive JNJ-67856633 until disease progression, intolerable toxicity, withdrawal of consent, or the investigator or sponsor decision. Subsequent dose levels will be assigned by the sponsor using an adaptive dose escalation strategy based on all available safety, pharmacokinetic (PK), and biomarker data.	Drug: JNJ-67856633; JNJ-67856633 capsule will be administered orally.
Experimental: Part 2 (Cohort Expansion): JNJ-67856633; Participants will receive JNJ-67856633 at the recommended Phase 2 dose (RP2D) determined in Part 1.	Drug: JNJ-67856633; JNJ-67856633 capsule will be administered orally.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Dose-Limiting Toxicity (DLT)	The DLTs are based on drug related adverse events and defined as any of the following events: any toxicity that would require discontinuation of treatment; and/or hematological / non-hematological toxicity of Grade 3 or higher.	Approximately 21 days
Part 1 and Part 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability	An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.	Up to 4 years and 11 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
JNJ-67856633 Plasma Concentrations	Concentration assessment will be done to evaluate the effect of JNJ-67856633.	Up to 4 years and 11 months
Part 1 and Part 2: Overall Response Rate (ORR)	ORR is defined as the percentage of participants who have a partial response (PR) and complete response (CR) according to the International Workshop on Chronic Lymphocytic Leukemia (iwCLL), non-Hodgkin lymphoma and Waldenstrom macroglobulinemia response criteria.	Up to 4 years and 11 months
Part 1 and Part 2: Complete Response Rate	Complete response rate is defined as the percentage of participants who achieve a best response of CR according to the iwCLL, non-Hodgkin lymphoma and Waldenstrom macroglobulinemia response criteria.	Up to 4 years and 11 months
Part 1 and Part 2: Time to Response (TTR)	TTR is defined for participants who achieved PR or CR as the time from the first dose of study drug to first response of PR or CR.	Up to 4 years and 11 months
Part 1 and Part 2: Duration of Response (DoR)	DoR is defined for participants who achieved PR or CR as the time between the date of initial documentation of PR or CR to the date of first documented evidence of disease progression or death, whichever comes first.	Up to 4 years and 11 months

Collaborators and Investigators

• Sponsor: Janssen Research & Development, LLC
• Investigators: Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC

Study record dates

Study Major Dates

• Study Start (Actual): April 3, 2019
• Primary Completion (Estimated): December 2, 2024
• Study Completion (Estimated): January 30, 2026

Study Registration Dates

• First Submitted: April 2, 2019
• First Submitted That Met QC Criteria: April 2, 2019
• First Posted (Actual): April 3, 2019

Study Record Updates

• Last Update Posted (Actual): March 27, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease Attributes; Hematologic Diseases; Leukemia, B-Cell; Chronic Disease; Lymphoma; Leukemia; Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell; Leukemia, Lymphoid
• Other Study ID Numbers: CR108587; 2018-003549-40 (EudraCT Number); 67856633LYM1001 (Other Identifier: Janssen Research & Development, LLC)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency.

As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No