IRB Study Number 24-721
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objectives
Dose escalation phase
To assess the safety and tolerability of ONO-4685 in patients with relapsed or refractory T-cell lymphoma
Expansion phase
To assess the safety of ONO-4685 in patients with relapsed or refractory T-cell lymphoma
Secondary Objectives
Dose escalation phase and Expansion phase
To assess preliminary efficacy, PK, and immunogenicity of ONO-4685 in patients with relapsed or refractory T-cell lymphoma
To assess optimal dose of ONO-4685 for further clinical evaluations
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 (the patient record or archive tissue result will be acceptable) confirmed diagnosis of one of the following subtypes of T-cell lymphoma as defined by the 2016 revision of the WHO classification of lymphoid malignancies:
a. PTCL: AITL, PTCL-NOS, nodal PTCL with TFH and follicular T-cell lymphoma (FTCL)
b. CTCL: MF and SS
Patients with CTCL stages II-B, III, and IV as defined by staging criteria (Olsen EA, 2011),
Relapsed or refractory patients with PTCL or CTCL:
a. Relapsed disease is defined when a patient progressed after achieving complete response (CR) or partial response (PR) with previous treatments
b. Refractory disease is defined when a patient failed to achieve a CR or PR after previous treatments
Patients must have received at least 2 prior systemic therapies. Patients eligible for CD30-directed therapy (e.g., brentuximab vedotin [BV]) will have BV as one of their systemic therapies,
Patients with PTCL must have either at least 1 measurable extranodal lesion with the longest diameter > 1.0 cm or at least 1 measurable nodal lesion with the longest diameter > 1.5 cm on fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) scan as defined by response criteria for PTCL (Cheson BD, 2014),
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 defined as:
a. ANC ≥ 1,000/mm3 (no white blood cell [WBC] growth factors for prior 14 days)
b. Platelets (PLT) ≥ 50,000/mm3 (no PLT transfusions for prior 14 days)
c. Absolute CD4 count > 200 cells/μL
d. Hemoglobin ≥ 8.0 g/dL (no red blood cell [RBC] transfusions for prior 14 days)
e. Total bilirubin ≤ 1.5 × upper limit of normal (ULN), or ≤ 3.0 × ULN if patient has a documented history of Gilbert’s syndrome or a genetic equivalent
f. Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase;[SGPT]) ≤ 3.0 × ULN
g. Calculated creatinine clearance ≥ 50 mL/min by the Cockcroft-Gault equation
Women of childbearing potential (including women who are amenorrheic due to chemical menopause or for another medical reason) must agree to use an effective method of contraception (Appendix 5 [Section 10.5.2]) from the time of informed consent to at least 4 months after the final dose of study treatment, and
Men must agree to use an effective method of contraception (Appendix 5 [Section 10.5.2]) from the start of study treatment until at least 4 months following the last dose of study treatment.
Exclusion Criteria
Patients with central nervous system (CNS) involvement,
Patients with ATLL,
Prior chemotherapy, therapeutic anti-cancer antibodies, or other anti-cancer therapies within 4 weeks (lenalidomide or mogamulizumab within 6 weeks) of the first dose of study treatment,
Prior autologous stem cell transplantation (ASCT) within 12 weeks of the first dose of study treatment,
Prior allogeneic stem cell transplant,
Prior radiotherapy within 4 weeks (localized palliative radiotherapy or total skin electron beam [TSEB] within 2 weeks) of the first dose of study treatment,
Patients with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 2 weeks of the first dose of study treatment except for inhaled or topical steroids treatment,
Patients participating in another clinical study with any investigational drug within 4 weeks prior to the first dose of study treatment,
Major surgery within 4 weeks prior to the first dose of study treatment or minor surgery (e.g., biopsy or surgery under topical anesthesia) within 2 weeks prior to the first dose of study treatment,
Live vaccine within 6 weeks prior to the first dose of study treatment,
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,
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 as follows, but not limited to:
a. Clinically significant cardiac disease (Class III or IV of the New York Heart Association functional classification)
b. Unstable angina pectoris within 6 months prior to the first dose of study treatment
c. Myocardial infarction within 6 months prior to the first dose of study treatment
d. Uncontrolled hypertension (sustained systolic blood pressure [BP] > 160 mm Hg or diastolic BP > 100 mm Hg) despite 2 anti-hypertensive medications
e. Unstable arrhythmia
f. Corrected QTc corrected with Fridericia’s formula (QTcF) interval > 480 mS
g. Stroke within 6 months prior to the first dose of study treatment
h. Left ventricular ejection fraction (LVEF) < 50%
i. Uncontrolled diabetes
Patients not recovered to Grade 1 or stabilized from the adverse effects (excluding alopecia) of any prior therapy for their malignancies, or
Women who are pregnant or lactating.
