Clinical trial NCT04657224: A Study of JNJ-64264681 and JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia
Official title: A Phase 1b, Open-Label Study of the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-64264681 in Combination With JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Lymphoma, Non-Hodgkin
Chronic Lymphocytic Leukemia
Lead sponsor: Janssen Research & Development, LLC
Sponsor class: INDUSTRY
First posted: 2020-12-08
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The primary purpose of this study is to determine: the recommended Phase 2 doses (RP2Ds) of JNJ-64264681 and JNJ 67856633 when administered together in participants with B cell non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) (Part A - Dose Escalation); and the safety of the RP2Ds for this combination in different histologies/participant populations (Part B - Cohort Expansion).

Detailed description: Bruton's tyrosine kinase (BTK) is a cytoplasmic tyrosine kinase that plays a critical role in B cell activation via the B cell receptor (BCR) signaling pathway. BTK is important for normal B-cell activation and the pathophysiology of B cell malignancies. A few BTK inhibitors have demonstrated clinical activity in non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Non-Hodgkin lymphoma represents a diverse set of diseases, of which more than 60 subtypes have been identified and classified by the world health organization. JNJ-64264681 is a second-generation, orally active, selective, and irreversible covalent inhibitor of BTK and JNJ-67856633 is an orally bioavailable, potent, and selective first in class mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) inhibitor that binds to an allosteric site on MALT1 with a mixed-type mechanism. JNJ-64264681 and JNJ-67856633 inhibit BTK and MALT1, respectively, and both BTK and MALT1 are involved in transmitting the pro-survival BCR signal. The study will consist of Screening Phase (28 days); Treatment Phase (from Cycle 1 Day 1 up to end of treatment, each cycle is a 21-day cycle) and a Follow-up Phase (from end of treatment visit until lost to follow-up, withdrawal of consent, death, 6 months after start of first subsequent antineoplastic therapy, after the clinical cut off (CCO) date participants will be withdrawn from the study 30 days after the last dose of study drugs were administered). The total study duration is estimated at 2 years and 2 months. Safety assessments will include physical examinations, vital signs, electrocardiograms, clinical safety laboratory assessments, eastern cooperative oncology group performance status, echocardiogram, and adverse events monitoring.

Eligibility criteria: Inclusion Criteria:

* Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1
* Cardiac parameters within the following range: corrected QT interval (QTcF) \<= 480 milliseconds
* Participants with B cell non-Hodgkin lymphoma (NHL) must have tumor tissue available at baseline as described in the protocol. This is not required for participants with chronic lymphocytic leukemia (CLL)
* Women of childbearing potential must agree to use a barrier method of contraception; use a highly effective preferably user-independent method of contraception; not to donate eggs (ova, oocytes) or freeze them for future use for the purposes of assisted reproduction during the study; not to plan to become pregnant; and not to breast-feed

Exclusion Criteria:

* Part A and select cohorts in Part B: Prior treatment with JNJ 64264681 or JNJ-67856633. Previously discontinued treatment with a Bruton's tyrosine kinase (BTK) or mucosa-associated lymphoid tissue lymphoma translocation protein (MALT) inhibitor other than JNJ 64264681 or JNJ-67856633 due to participant or doctor choice without evidence of progression or intolerable class-related toxicity will be eligible
* Known (active) central nervous system (CNS) involvement
* Received prior solid organ transplantation
* Participant has known allergies, hypersensitivity, or intolerance to JNJ-64264681 or JNJ 67856633 or excipients
* Toxicities from previous anti-cancer therapies that have not resolved to baseline levels, or to Grade less than (\<) 2 (except for alopecia \[\>=Grade 2\], vitiligo \[Grade 2\] and peripheral neuropathy \[Grade 1\])

Primary outcomes:
measure: Part A: Number of Participants with Dose-limiting Toxicity (DLT)
timeFrame: Up to 28 days
measure: Part A and Part B: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
timeFrame: Up to 3 years and 9 months
Secondary outcomes:
measure: Plasma Concentrations of JNJ-64264681 and JNJ-67856633
timeFrame: Up to 3 years and 9 months
measure: Bruton's Tyrosine Kinase (BTK) Occupancy in Peripheral Blood Mononuclear Cell (PBMCs)
timeFrame: Up to 3 years and 9 months
measure: Overall Response Rate (ORR)
timeFrame: Up to 3 years and 9 months
measure: Time to First Response
timeFrame: Up to 3 years and 9 months
measure: Duration of Response
timeFrame: Up to 3 years and 9 months
Other outcomes:
Locations:
city: Stony Brook
country: United States
facility: Stony Brook University Medical Center
state: New York
city: Clayton
country: Australia
facility: Monash Medical Centre
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
city: Nedlands
country: Australia
facility: Linear Clinical Research Ltd
city: Randwick
country: Australia
facility: Scientia Clinical Research
city: Brugge
country: Belgium
facility: AZ St.-Jan Brugge-Oostende AV
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent - UZ GENT
city: Yvoir
country: Belgium
facility: CHU UCL Namur - Site Godinne
city: Lille
country: France
facility: CHRU de Lille Hopital Claude Huriez
city: Nantes Cedex 1
country: France
facility: Chu Hotel Dieu
city: Pierre Benite
country: France
facility: Centre hospitalier Lyon-Sud
city: Tours Cedex 9
country: France
facility: CHU Bretonneau
city: Tbilisi
country: Georgia
facility: Arensia Exploratory Medicine
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Tel Aviv
country: Israel
facility: Tel Aviv Sourasky MC
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Chisinau
country: Moldova, Republic of
facility: Arensia Exploratory Medicine
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne
city: Katowice
country: Poland
facility: Pratia Onkologia Katowice
city: Krakow
country: Poland
facility: Pratia MCM Krakow
city: Skorzewo
country: Poland
facility: Centrum Medyczne Pratia Poznan
city: Barcelona
country: Spain
facility: Hosp Univ Vall D Hebron
city: Madrid
country: Spain
facility: Hosp Univ Fund Jimenez Diaz
city: Kyiv
country: Ukraine
facility: Medical Center of Limited Liability Company Arensia Exploratory Medicine
Study officials:
affiliation: Janssen Research & Development, LLC
name: Janssen Research & Development, LLC Clinical Trials
role: STUDY_DIRECTOR
References: