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

Phase 1
Active, not recruiting
Conditions
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Non-Hodgkin
Interventions
Registration Number
NCT05515406
Lead Sponsor
Ono Pharmaceutical Co. Ltd
Brief Summary

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

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.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
All
Target Recruitment
108
Inclusion Criteria
  1. Patient aged ≥ 18 years
  2. Written informed consent by the patient or the patient's legally authorized representative
  3. Patient with histologically/cytologically confirmed diagnosis of NHL or CLL
  4. Patient with relapsed or refractory disease who has no available therapeutic options known to provide clinical benefit
  5. Patient who has measurable disease
  6. All acute toxic effects of any prior antitumor therapy, including investigational therapy, resolved to Grade ≤ 1 before the start of study therapy
  7. Eastern Cooperative Oncology Group Performance Status 0 to 2
  8. Adequate bone marrow, renal and hepatic functions
Exclusion Criteria
  1. History of lymphoid malignancy other than those allowed per inclusion criteria
  2. Patient with central nervous system involvement
  3. Patient with systemic and active infection
  4. 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
  5. Prior treatment with a MALT1 inhibitor
  6. Patient receiving any other investigational drug within 4 weeks prior to study entry
  7. Patient is unable to swallow tablets
  8. Patient is found to be otherwise ineligible for the study by the investigator or sub investigator

Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Dose Expansion Phase (Part 2)ONO-7018Eligible patients will be assigned to the recommended dose level(s) selected from Part 1.
Dose Escalation Phase (Part 1)ONO-7018Up 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.
Primary Outcome Measures
NameTimeMethod
Estimate of Maximum Tolerated Dose (MTD)Up to 3 weeks

MTD will be estimated based on Dose limiting toxicity (DLT) observed during the first 3 weeks of treatment

Incidence, causality, and severity of Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs)Through study completion, an average of 1 year

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.

Secondary Outcome Measures
NameTimeMethod
Antitumor Activity of ONO-7018 (Overall Response Rate [ORR])Through study completion, an average of 1 year

Antitumor activity of ONO-7018 as measured by ORR will be assessed according to the response criteria for Lymphoma.Lymphoma.

Plasma Concentration of ONO-7018Up to 48 weeks

Plasma concentration will be assessed to evaluate Pharmacokinetics

Antitumor Activity of ONO-7018 (Duration of Response [DOR])Through study completion, an average of 1 year

Antitumor activity of ONO-7018 as measured by DOR will be assessed according to the response criteria for Lymphoma.

Antitumor Activity of ONO-7018 (Overall Survival [OS])Through study completion, an average of 1 year

Antitumor activity of ONO-7018 as measured by OS will be assessed.

Antitumor Activity of ONO-7018 (Progression Free Survival [PFS])Through study completion, an average of 1 year

Antitumor activity of ONO-7018 as measured by PFS will be assessed according to the response criteria for Lymphoma.

Trial Locations

Locations (10)

MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

Northwest Medical Specialities

🇺🇸

Tacoma, Washington, United States

Jonsson Comprehensive Cancer Center

🇺🇸

Santa Monica, California, United States

AMR Kansas City

🇺🇸

Kansas City, Missouri, United States

Leo Jenkins Cancer Center/ECU School of Medicine

🇺🇸

Greenville, North Carolina, United States

University of Cincinnati

🇺🇸

Cincinnati, Ohio, United States

University of Pennsylvania

🇺🇸

Philadelphia, Pennsylvania, United States

Thomas Jefferson University

🇺🇸

Philadelphia, Pennsylvania, United States

Sarah Cannon Research Institute

🇺🇸

Nashville, Tennessee, United States

Baylor Scott & White Research Institute

🇺🇸

Dallas, Texas, United States

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