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

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

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).

Study Overview

• Status: Terminated
• Conditions: Lymphoma, Non-Hodgkin; Leukemia, Lymphocytic, Chronic, B-Cell
• Intervention / Treatment: Drug: ONO-7018

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Santa Monica, California, United States, 90404
      • Jonsson Comprehensive Cancer Center
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • AMR Kansas City
  • New Jersey
    • Florham Park, New Jersey, United States, 07932
      • Summit Medical Group
  • North Carolina
    • Greenville, North Carolina, United States, 27858
      • Leo Jenkins Cancer Center/ECU School of Medicine
  • Ohio
    • Cincinnati, Ohio, United States, 45267
      • University of Cincinnati
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor Scott & White Research Institute
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center
  • Washington
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialities

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose Escalation Phase (Part 1); 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; ONO-7018 tablet(s) are administered orally
Experimental: Dose Expansion Phase (Part 2); Eligible patients will be assigned to the recommended dose level(s) selected from Part 1.	Drug: ONO-7018; ONO-7018 tablet(s) are administered orally

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ono Pharmaceutical Co., Ltd.
• Investigators: Study Director: Project Leader, Ono Pharma USA Inc

Study record dates

Study Major Dates

• Study Start (Actual): February 13, 2023
• Primary Completion (Actual): August 13, 2025
• Study Completion (Actual): August 13, 2025

Study Registration Dates

• First Submitted: August 18, 2022
• First Submitted That Met QC Criteria: August 23, 2022
• First Posted (Actual): August 25, 2022

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: ONO-7018, MALT1 inhibitor, Lymphoma, Leukemia
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Chronic Disease; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, B-Cell; Leukemia, Lymphoid; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Leukemia; Lymphoma; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: ONO-7018-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No