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
Overview
- Phase
- Phase 1
- Intervention
- JNJ-67856633
- Conditions
- Leukemia, Lymphocytic, Chronic, B-Cell
- Sponsor
- Janssen Research & Development, LLC
- Enrollment
- 226
- Locations
- 47
- Primary Endpoint
- Part 1 and Part 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
- Status
- Completed
- Last Updated
- 10 months ago
Overview
Brief Summary
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.
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.
Investigators
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 (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
Arms & Interventions
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.
Intervention: JNJ-67856633
Part 2 (Cohort Expansion): JNJ-67856633
Participants will receive JNJ-67856633 at the recommended Phase 2 dose (RP2D) determined in Part 1.
Intervention: JNJ-67856633
Outcomes
Primary Outcomes
Part 1 and Part 2: Number of Participants with Adverse Events (AEs) as a Measure of Safety and Tolerability
Time Frame: Up to 4 years and 11 months
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.
Part 1: Dose-Limiting Toxicity (DLT)
Time Frame: Approximately 21 days
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.
Secondary Outcomes
- Part 1 and Part 2: Overall Response Rate (ORR)(Up to 4 years and 11 months)
- JNJ-67856633 Plasma Concentrations(Up to 4 years and 11 months)
- Part 1 and Part 2: Complete Response Rate(Up to 4 years and 11 months)
- Part 1 and Part 2: Time to Response (TTR)(Up to 4 years and 11 months)
- Part 1 and Part 2: Duration of Response (DoR)(Up to 4 years and 11 months)