A Study of JNJ-64264681 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia

Study Overview
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Brief Summary
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The purpose of the study is to determine the recommended Phase 2 dose(s) (RP2D[s]) in B cell non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) in Part 1 and to evaluate the safety of JNJ-64264681 at the RP2D(s) in Part 2.

Official Title
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A Phase 1, Open-Label Study of the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-64264681 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia

Conditions
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Lymphoma, Non-Hodgkin, Leukemia, Lymphocytic, Chronic, B-Cell

Intervention / Treatment
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* Drug: JNJ-64264681


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 Participants must have cardiac parameters within the following range: corrected QT interval (QTcF) less than or equal to <= 480 milliseconds based on the average of triplicate assessments performed as close as possible in succession (the full set of triplicates should be completed in less than 10 minutes) Women of childbearing potential must have a negative highly sensitive serum pregnancy test (example: beta human chorionic gonadotropin [beta-hCG]) at screening, and a negative serum or urine pregnancy test prior to the first dose of study drug Women must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for a period of at least 30 days after the last study drug administration Participants must be willing and able to adhere to the lifestyle restrictions specified in this protocol Exclusion Criteria: Participant has known active central nervous system (CNS) involvement Participant has received prior solid organ transplantation Participant has known allergies, hypersensitivity, or intolerance to JNJ-64264681 or its excipients Participant has been treated with an investigational drug (including investigational vaccines) within five half-lives or 2 weeks before the planned first dose of study drug Participant is experiencing toxicities from previous anticancer therapies that have not resolved to baseline levels, or to Grade 1 or less (except for alopecia and peripheral neuropathy)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: JNJ-64264681: Dose Escalation and Expansion<br>Participants will receive oral administration of JNJ-64264681 capsule at a dose assigned by the sponsor Study Evaluation Team (SET), based on the available safety, pharmacokinetics, and pharmacodynamics data in dose escalation treatment group (Part 1); and recommended Phase 2 dose (RP2D) determined in Part 1 in cohort expansion treatment group (Part 2). | Drug: JNJ-64264681<br>* JNJ-64264681 capsule will be administered orally.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Number of Participants With Dose Limiting Toxicity (DLT) | The DLTs are based on drug related adverse events and defined as any of the following events: hematological or non-hematological toxicity of grade 3 or higher (as specified in protocol). | Up to 21 days | 
| Part 1 and Part 2: Number of Participants with Adverse Events (AEs) | 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 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Concentration of JNJ-64264681 | Plasma concentration of JNJ-64264681 will be evaluated. | Up to 2 years | 
| Percentage Occupancy of the Target | The pharmacodynamics of JNJ-64264681 will be assessed by determining the percentage of target occupancy. Blood samples will be obtained for pharmacodynamic assessments (target occupancy). | Up to 2 years | 
| Overall Response Rate (ORR) | ORR is defined as the percentage of participants who achieve a complete response (CR) + partial response (PR) or better according to the Revised Response Criteria for Malignant Lymphoma and the International Workshop on Chronic Lymphocytic Leukemia (iwCLL) Response Criteria and International Workshop for Waldenstrom Macroglobulinemia (IWWM) Response Criteria. | Up to 2 years | 
| 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 according to the Revised Response Criteria for Malignant Lymphoma and iwCLL Response Criteria and IWWM Response Criteria. | Up to 2 years | 
| 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 either the first documented evidence of disease progression or death according to the Revised Response Criteria for Malignant Lymphoma and iwCLL Response Criteria and IWWM Response Criteria. | Up to 2 years | 
| Complete Response (CR) Rate | CR rate is defined as the percentage of participants who achieve a best response of CR according to the Revised Response Criteria for Malignant Lymphoma and iwCLL Response Criteria and IWWM Response Criteria. | Up to 2 years | 
| Progression-free Survival (PFS) | PFS is defined as the time from the date of the first dose of the study drug to the date of either the first documented disease progression (according to the Revised Response Criteria for Malignant Lymphoma and iwCLL Response Criteria and IWWM Response Criteria), or death due to any cause. | Up to 2 years |