Valemetostat Tosylate (DS-3201b), an Enhancer of Zeste Homolog (EZH) 1/2 Dual Inhibitor, for Relapsed/Refractory Peripheral T-Cell Lymphoma (VALENTINE-PTCL01)
Valemetostat Tosylate (DS-3201b), an Enhancer of Zeste Homolog (EZH) 1/2 Dual Inhibitor, for Relapsed/Refractory Peripheral T-Cell Lymphoma (VALENTINE-PTCL01)
This study will characterize the safety and clinical benefit of valemetostat tosylate in
 participants with relapsed/refractory peripheral T-cell lymphoma, including
 relapsed/refractory adult T-cell leukemia/lymphoma.
This study was designed to evaluate the efficacy and safety of valemetostat tosylate
 monotherapy. The primary objective will evaluate objective response rate of valemetostat
 tosylate monotherapy as measured by blinded independent central review (BICR) in
 relapsed/refractory peripheral T-cell lymphoma, including relapsed/refractory adult T-cell
 leukemia/lymphoma participants.
Inclusion Criteria:

 -  Written informed consent

 -  Participants ≥18 years of age or the minimum legal adult age (whichever is greater) at
 the time the informed consent form is signed.

 -  Eastern Cooperative Oncology Group performance status of 0, 1, or 2

 -  Cohort 1 relapsed/refractory peripheral T-cell lymphoma (PTCL):

 -  Should be pathologically confirmed by the local pathologist/investigators; local
 histological diagnosis will be used for eligibility determination. Participants
 with the following subtypes of PTCL are eligible according to 2016 WHO
 classification prior to the initiation of study drug. Any T-cell lymphoid
 malignancies not listed are excluded. Eligible subtypes include:

 -  Enteropathy-associated T-cell lymphoma

 -  Monomorphic epitheliotropic intestinal T-cell lymphoma

 -  Hepatosplenic T-cell lymphoma

 -  Primary cutaneous T-cell lymphoma

 -  Primary cutaneous CD8+ aggressive epidermotropic cytotoxic T-cell lymphoma

 -  PTCL, not otherwise specified

 -  Angioimmunoblastic T-cell lymphoma

 -  Follicular T-cell lymphoma

 -  Nodal PTCL with T-follicular helper (TFH) phenotype

 -  Anaplastic large cell lymphoma, ALK positive

 -  Anaplastic large cell lymphoma, ALK negative

 -  Cohort 2 relapsed/refractory adult T-cell leukemia/lymphoma (ATL) acute, lymphoma, or
 unfavorable chronic type. Relapsed/refractory ATL should be pathologically or
 hematocytologically confirmed by the local pathologist/investigators; local
 histological/hematocytological diagnosis will be used for eligibility determination.
 The positivity of anti-human T-cell leukemia virus type 1 (HTLV-1) antibody will be
 locally determined for eligibility.

 -  Must have at least one lesion which is measurable in 2 perpendicular dimensions on
 computed tomography (or magnetic resonance imaging) based on local radiological read

 -  Documented refractory, relapsed, or progressive disease after at least 1 prior line of
 systemic therapy.

 -  Refractory is defined as:

 -  Failure to achieve CR (or CRu for ATL) after first-line therapy

 -  Failure to reach at least PR after second-line therapy or beyond

 -  Must have at least 1 prior line of systemic therapy for PTCL or ATL.

 -  Participants must be considered hematopoietic cell transplantation (HCT)
 ineligible during screening due to disease status (active disease),
 comorbidities, or other factors; the reason for HCT ineligibility must be clearly
 documented.

 -  In the PTCL cohort, participants with anaplastic large cell lymphoma (ALCL) must
 have prior brentuximab vedotin treatment.

 Exclusion Criteria:

 Participants meeting any exclusion criteria for this study will be excluded from this
 study. Below is a list of the key exclusion criteria:

 -  Diagnosis of mycosis fungoides, Sézary syndrome and primary cutaneous ALCL, and
 systemic dissemination of primary cutaneous ALCL

 -  Diagnosis of precursor T-cell lymphoblastic leukemia and lymphoma (T-cell acute
 lymphoblastic leukemia and T-cell lymphoblastic lymphoma), T-cell prolymphocytic
 leukemia, or T-cell large granular lymphocytic leukemia

 -  Prior malignancy active within the previous 2 years except for locally curable cancer
 that is currently considered as cured, such as cutaneous basal or squamous cell
 carcinoma, superficial bladder cancer, or cervical carcinoma in situ, or an incidental
 histological finding of prostate cancer.

 -  Presence of active central nervous system involvement of lymphoma

 -  History of autologous HCT within 60 days prior to the first dose of study drug

 -  History of allogeneic HCT within 90 days prior to the first dose of study drug

 -  Clinically significant graft-versus-host disease (GVHD) or GVHD requiring systemic
 immunosuppressive prophylaxis or treatment

 -  Inadequate washout period from prior lymphoma-directed therapy before enrollment,
 defined as follows:

 -  Prior systemic therapy (eg, chemotherapy, immunomodulatory therapy, or monoclonal
 antibody therapy) within 3 weeks prior to the first dose of study drug

 -  Had curative radiation therapy or major surgery within 4 weeks or palliative
 radiation therapy within 2 weeks prior to the first dose of study drug

 -  Uncontrolled or significant cardiovascular disease, including:

 -  Evidence of prolongation of QT/QTc interval (eg, repeated episodes of QT
 corrected for heart rate using Fridericia's method >450 ms) (average of
 triplicate determinations)

 -  Diagnosed or suspected long QT syndrome or known family history of long QT
 syndrome

 -  History of clinically relevant ventricular arrhythmias, such as ventricular
 tachycardia, ventricular fibrillation, or Torsade de Pointes

 -  Uncontrolled arrhythmia (subjects with asymptomatic, controllable atrial
 fibrillation may be enrolled) or asymptomatic persistent ventricular tachycardia

 -  Participant has clinically relevant bradycardia of <50 bpm, unless the
 participant has a pacemaker

 -  History of second- or third-degree heart block. Candidates with a history of
 heart block may be eligible if they currently have pacemakers and have no history
 of fainting or clinically relevant arrhythmia with pacemakers within 6 months
 prior to Screening

 -  Myocardial infarction within 6 months prior to Screening

 -  Angioplasty or stent craft implantation within 6 months prior to Screening

 -  Uncontrolled angina pectoris within 6 months prior to Screening

 -  New York Heart Association Class 3 or 4 congestive heart failure

 -  Coronary/peripheral artery bypass graft within 6 months prior to Screening

 -  Uncontrolled hypertension (resting systolic blood pressure >180 mmHg or diastolic
 blood pressure >110 mmHg)

 -  Complete left or right bundle branch block

 -  History of treatment with other EZH inhibitors

 -  Current use of moderate or strong cytochrome P450 (CYP)3A inducers

 -  Systemic treatment with corticosteroids (>10 mg daily prednisone equivalents). Note:
 Short-course systemic corticosteroids (eg, prevention/treatment for transfusion
 reaction) or use for a non-cancer indication (eg, adrenal replacement) is permissible.