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

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