A Study to Investigate the Safety, Tolerability, PK, PD, and Efficacy of ONO-7018 in Patients With R/R NHL or CLL

Study Overview
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Brief Summary
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This is a Phase 1, open-label, multicenter study. This will be the first-in-human clinical study for ONO-7018 and will be conducted in two phases: a Dose Escalation Phase (Part 1) and a Dose Expansion Phase (Part 2).

Detailed Description
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ONO-7018 is a selective inhibitor of mucosa associated lymphoid tissue protein 1 (MALT1) and is expected to exhibit antitumor activity in NHL and CLL. The purpose of this study is to determine the MTD and to evaluate the safety, tolerability, PK, pharmacodynamics (biomarkers), and efficacy of ONO-7018 in patients with relapsed or refractory NHL or CLL.

Official Title
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A Phase I, Open-label, Dose Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of ONO-7018 in Patients With Relapsed or Refractory NHL or CLL

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

Intervention / Treatment
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* Drug: ONO-7018
* Drug: ONO-7018


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient aged ≥ 18 years Written informed consent by the patient or the patient's legally authorized representative Patient with histologically/cytologically confirmed diagnosis of NHL or CLL Patient with relapsed or refractory disease who has no available therapeutic options known to provide clinical benefit Patient who has measurable disease All acute toxic effects of any prior antitumor therapy, including investigational therapy, resolved to Grade ≤ 1 before the start of study therapy Eastern Cooperative Oncology Group Performance Status 0 to 2 Adequate bone marrow, renal and hepatic functions Exclusion Criteria: History of lymphoid malignancy other than those allowed per inclusion criteria Patient with central nervous system involvement Patient with systemic and active infection Any serious or uncontrolled medical disorder that may increase the risk associated with study participation or study treatment, or interfere with the interpretation of study results Prior treatment with a MALT1 inhibitor Patient receiving any other investigational drug within 4 weeks prior to study entry Patient is unable to swallow tablets Patient is found to be otherwise ineligible for the study by the investigator or sub investigator

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
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation Phase (Part 1)<br>Up to 4 dose levels will be evaluated. Eligible patients will be assigned to a dose level cohort according to a traditional 3+3 dose escalation design. | Drug: ONO-7018<br>* ONO-7018 tablet(s) are administered orally<br>|
| Experimental: Dose Expansion Phase (Part 2)<br>Eligible patients will be assigned to the recommended dose level(s) selected from Part 1. | Drug: ONO-7018<br>* ONO-7018 tablet(s) are administered orally<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimate of Maximum Tolerated Dose (MTD) | MTD will be estimated based on Dose limiting toxicity (DLT) observed during the first 3 weeks of treatment | Up to 3 weeks | 
| Incidence, causality, and severity of Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs) | Adverse events with the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 used as a guide for the grading of severity. | Through study completion, an average of 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Concentration of ONO-7018 | Plasma concentration will be assessed to evaluate Pharmacokinetics | Up to 48 weeks | 
| Antitumor Activity of ONO-7018 (Overall Response Rate [ORR]) | Antitumor activity of ONO-7018 as measured by ORR will be assessed according to the response criteria for Lymphoma.Lymphoma. | Through study completion, an average of 1 year | 
| Antitumor Activity of ONO-7018 (Duration of Response [DOR]) | Antitumor activity of ONO-7018 as measured by DOR will be assessed according to the response criteria for Lymphoma. | Through study completion, an average of 1 year | 
| Antitumor Activity of ONO-7018 (Progression Free Survival [PFS]) | Antitumor activity of ONO-7018 as measured by PFS will be assessed according to the response criteria for Lymphoma. | Through study completion, an average of 1 year | 
| Antitumor Activity of ONO-7018 (Overall Survival [OS]) | Antitumor activity of ONO-7018 as measured by OS will be assessed. | Through study completion, an average of 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ONO-7018, MALT1 inhibitor, Lymphoma, Leukemia