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

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

Official Title
-----------------
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

Conditions
-----------------
Relapsed or Refractory T Cell Lymphoma

Intervention / Treatment
-----------------
* Drug: ONO-4685


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria Patients aged ≥ 18 years at time of screening Written informed consent by the patient or the patients' legally authorized representative prior to screening Patients with histologically or cytologically confirmed diagnosis of one of the following subtypes of T-cell lymphoma: 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) Cutaneous T-cell lymphoma (CTCL) (stages II-B, III, and IV): Mycosis fungoides (MF) and Sezary syndrome (SS) Patients must have received at least 2 prior systemic therapies. Patients with PTCL must have at least 1 measurable lesion Patients with CTCL must have assessable disease by response criteria for CTCL (Olsen EA, 2011) Eastern Cooperative Oncology Group Performance Status (ECOG PS) = 0-2 Life expectancy of at least 3 months Adequate bone marrow, renal and hepatic functions Exclusion Criteria: Patients with central nervous system (CNS) involvement Patients with Adult T-cell leukemia/lymphoma (ATLL) Prior allogeneic stem cell transplant 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 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 History of severe allergy or hypersensitivity to any monoclonal antibodies, other therapeutic proteins or corticosteroid (e.g., dexamethasone) History of infection with Mycobacterium tuberculosis within 2 years prior to the first dose of study treatment Patients with systemic and active infection including human immunodeficiency virus (HIV), hepatitis B or C virus infection Patients not recovered to Grade 1 or stabilized from the adverse effects (excluding alopecia) of any prior therapy for their malignancies Women who are pregnant or lactating

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ONO-4685 monotherapy<br>Patients with relapsed or refractory T cell Lymphoma who meet eligibility criteria will be enrolled to receive ONO-4685 monotherapy | Drug: ONO-4685<br>* ONO-4685 is administered by IV infusion. The administration of ONO-4685 will be continued until disease progression or unacceptable toxicity is observed<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
CD3, ONO-4685, PD-1, Bispecific antibody, PTCL, AITL, PTCL-NOS, nodal PTCL with TFH, FTCL, CTCL, MF, SS