A Study of ONO-7018 in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma

A Phase 1, Open-label, Dose Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of ONO-7018 in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma (NHL) in Japan

ONO-7018 is a selective inhibitor of mucosa associated lymphoid tissue protein 1 (MALT1) and is expected to exhibit antitumor activity in NHL. This study is Phase1 study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (biomarkers) and efficacy of ONO-7018 in patients with relapsed or refractory NHL.

Study Overview

• Status: Active, not recruiting
• Conditions: Non Hodgkin Lymphoma
• Intervention / Treatment: Drug: ONO-7018

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Osaka, Japan
    • National Hospital Organization Osaka National Hospital
  • Aichi
    • Nagoya-shi, Aichi, Japan
      • Nagoya City University Hospital
  • Gumma
    • Shibukawa-shi, Gumma, Japan
      • National Hospital Organization Shibukawa Medical Center
  • Hiroshima
    • Hiroshima-shi, Hiroshima, Japan
      • Hiroshima Red Cross Hospital Atomic-bomb Survivors Hospital
  • Miyagi
    • Sendai-shi, Miyagi, Japan
      • National Hospital Organization Sendai Medical Center
  • Tokyo
    • Koto-ku, Tokyo, Japan
      • The Cancer Institute Hospital of JFCR

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patient with histologically/cytologically confirmed diagnosis of any of the subtypes of B-cell NHL or T-cell NHL defined below as documented by medical records and with histology based on criteria established by the World Health Organization (Swerdlow 2017)
2. Relapsed or refractory patient who is refractory or intolerant to standard therapy or for whom, in the opinion of the investigator, there is no appropriate treatment for the primary disease.
3. Patient who has measurable disease
4. Eastern Cooperative Oncology Group Performance Status 0 to 2
5. Life expectancy of at least 3 months

Exclusion Criteria:

1. 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
2. Patient with malignancies other than lymphoid malignancy allowed per inclusion criteria
3. Prior treatment with a MALT1 inhibitor
4. Patient is unable to swallow tablets

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Evaluation of Tolerability; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicities	Observed toxicities will be graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v5.0 to assess the tolerability of ONO-7018.	up to 3 weeks after the first dose
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.	Up to 28 days after the last dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentration of ONO-7018	Plasma concentration will be assessed to evaluate Pharmacokinetics.	up to 16 weeks after the first dose
Maximum observed concentration (Cmax)	To assess the PK profile of ONO-7018	up to 16 weeks after the first dose
Time to Cmax (Tmax)	To assess the PK profile of ONO-7018	up to 16 weeks after the first dose
Area under the concentration-time curve to the end of the dosing period (AUCtau)	To assess the PK profile of ONO-7018	up to 16 weeks after the first dose
Elimination half-life (T1/2)	To assess the PK profile of ONO-7018	up to 16 weeks after the first dose
Predose trough concentration (Ctrough)	To assess the PK profile of ONO-7018	up to 16 weeks after the first dose
Overall Response Rate (ORR)	Antitumor activity of ONO-7018 as measured by ORR will be assessed according to the response criteria for Lymphoma.	through study completion, an average of 1 year
Complete response rate (CRR)	Antitumor activity of ONO-7018 as measured by CRR will be assessed according to the response criteria for Lymphoma.	through study completion, an average of 1 year
Best overall response (BOR)	Antitumor activity of ONO-7018 as measured by BOR will be assessed according to the response criteria for Lymphoma.	through study completion, an average of 1 year
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
Time to response (TTR)	Antitumor activity of ONO-7018 as measured by TTR will be assessed according to the response criteria for Lymphoma.	through study completion, an average of 1 year
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
Overall survival (OS)	Antitumor activity of ONO-7018 as measured by OS will be assessed.	through study completion, an average of 1 year
Percent change of tumor volume	Percent change of tumor volume will be assessed according to the response criteria for Lymphoma in order to evaluate antitumor activity of ONO-7018.	through study completion, an average of 1 year
Maximum percent reduction of tumor volume	Maximum percent reduction of tumor volume will be assessed according to the response criteria for Lymphoma in order to evaluate antitumor activity of ONO-7018.	through study completion, an average of 1 year

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): November 27, 2024
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: September 29, 2024
• First Submitted That Met QC Criteria: September 29, 2024
• First Posted (Actual): October 2, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 16, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin
• Other Study ID Numbers: ONO-7018-03; jRCT2021240028 (Registry Identifier: Registry Identifier:)

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