Study of ONO-4685 in Patients With Relapsed or Refractory T Cell Lymphoma

An Open-label, Multi-center, Non-randomized Phase I Dose Escalation Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of ONO-4685 Given as Monotherapy in Patients With Relapsed or Refractory T Cell Lymphoma

This study will investigate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ONO-4685 in patients with relapsed or refractory T cell Lymphoma

Study Overview

• Status: Recruiting
• Conditions: Relapsed or Refractory T Cell Lymphoma
• Intervention / Treatment: Drug: ONO-4685

• Study Type: Interventional
• Enrollment (Estimated): 217
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: North America Clinical Trial Support Desk; Phone Number: +18665877745(Toll-Free); Email: clinical_trial@ono-pharma.com
• Study Contact Backup: Name: International Clinical Trial Support Desk; Phone Number: +17162141777(Standard); Email: clinical_trial@ono-pharma.com

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Completed
      • University of Alabama at Birmingham
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope
    • Orange, California, United States, 92868
      • Recruiting
      • University of California Irvine Medical Center - Chao Family Comprehensive Cancer Center
    • Palo Alto, California, United States, 94304
      • Recruiting
      • Stanford Cancer Institute
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • Recruiting
      • Yale Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Winship Cancer Institute of Emory University
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Recruiting
      • Karmanos Cancer Institute
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University School of Medicine in St. Louis
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • Hackensack University Medical Center - John Theurer Cancer Center
  • New York
    • Buffalo, New York, United States, 14263
      • Recruiting
      • Roswell Park Cancer Institute
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan-Kettering Cancer Center
    • New York, New York, United States, 10032
      • Recruiting
      • New York-Presbyterian/Columbia University Irving Medical Center - Herbert Irving Comprehensive Cancer Center (HICCC)
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Novant Health Presbyterian Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Recruiting
      • Cleveland Clinic
  • Oregon
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health & Science University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania - Perelman Center
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt University - Ingram Cancer Center
  • Texas
    • Dallas, Texas, United States, 75390
      • Recruiting
      • UT Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Recruiting
      • MD Anderson

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria

1. Patients aged ≥ 18 years at time of screening
2. Written informed consent by the patient or the patients' legally authorized representative prior to screening

3. Patients with histologically or cytologically confirmed diagnosis of one of the following subtypes of T-cell lymphoma:

   1. Peripheral T-cell lymphoma (PTCL): Angioimmunoblastic T-cell lymphoma (AITL), PTCL, not otherwise specified (PTCL-NOS), nodal PTCL with T-follicular helper (TFH) and follicular T-cell lymphoma (FTCL)
   2. Cutaneous T-cell lymphoma (CTCL) (stages II-B, III, and IV): Mycosis fungoides (MF) and Sezary syndrome (SS)
4. Patients must have received at least 2 prior systemic therapies
5. Patients with PTCL must have at least 1 measurable lesion (Cheson BD, 2014)
6. Patients with CTCL must have assessable disease by response criteria for CTCL (Olsen EA, 2011)
7. Eastern Cooperative Oncology Group Performance Status (ECOG PS) = 0-2
8. Life expectancy of at least 3 months
9. Adequate bone marrow, renal and hepatic functions

Exclusion Criteria:

1. Patients with central nervous system (CNS) involvement
2. Patients with Adult T-cell leukemia/lymphoma (ATLL)
3. Prior allogeneic stem cell transplant
4. Prior treatment with ONO-4685, anti-PD-1, anti-PD-L1, anticytotoxic T lymphocyte associated protein 4 (CTLA-4) antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
5. Prior allogeneic and autologous chimeric antigen receptor (CAR) T-cell therapy
6. Patients with malignancies (other than T-cell lymphoma) except for completely resected basal cell carcinoma, stage I squamous cell carcinoma, carcinoma in situ, or any other malignancies that has not relapsed for at least 2 years
7. History of severe allergy or hypersensitivity to any monoclonal antibodies, other therapeutic proteins or corticosteroid (e.g., dexamethasone)
8. History of infection with Mycobacterium tuberculosis within 2 years prior to the first dose of study treatment
9. Patients with systemic and active infection including human immunodeficiency virus (HIV), hepatitis B or C virus infection
10. Patients not recovered to Grade 1 or stabilized from the adverse effects (excluding alopecia) of any prior therapy for their malignancies
11. Women who are pregnant or lactating

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: ONO-4685 monotherapy; Patients with relapsed or refractory T cell Lymphoma who meet eligibility criteria will be enrolled to receive ONO-4685 monotherapy	Drug: ONO-4685; ONO-4685 is administered by IV infusion. The administration of ONO-4685 will be continued until disease progression or unacceptable toxicity is observed

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence, nature, 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
Estimate of Maximum Tolerate Dose (MTD)	MTD will be estimated based on Dose limiting toxicity (DLT) observed during the first 3 weeks of treatment	Up to 3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma Concentration of ONO-4685	Plasma concentration will be assessed to evaluate Pharmacokinetics	Up to 48 weeks
Plasma Concentration of Anti-Drug Antibody (ADA)	ADA to ONO-4685 will be assessed to evaluate potential immunogenicity.	Up to 48 weeks
Antitumor Activity of ONO-4685	Antitumor Activity of ONO-4685 will be assessed according to the response criteria for Lymphoma.	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): December 10, 2021
• Primary Completion (Estimated): August 31, 2027
• Study Completion (Estimated): August 31, 2028

Study Registration Dates

• First Submitted: September 30, 2021
• First Submitted That Met QC Criteria: October 14, 2021
• First Posted (Actual): October 15, 2021

Study Record Updates

• Last Update Posted (Actual): February 13, 2026
• Last Update Submitted That Met QC Criteria: February 11, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: PTCL; PD-1; MF; CTCL; AITL; Bispecific antibody; PTCL-NOS; SS; ONO-4685; FTCL; CD3; nodal PTCL with TFH
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease Attributes; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Pathological Conditions, Signs and Symptoms; Hemic and Lymphatic Diseases; Recurrence; Lymphoma, T-Cell
• Other Study ID Numbers: ONO-4685-03

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