Valemetostat tosylate for Peripheral T-cell lymphoma | Adult T-cell leukaemia/lymphoma (ATL)

Inclusion criteria

• {"criterion_text":"- Written informed consent\n- Subjects ≥18 years of age or the minimum legal adult age (whichever is greater) at the time the ICF is signed.\n- Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2\n- Cohort 1 (R/R PTCL): Diagnosis should be confirmed by the local pathologist; local histological diagnosis will be used for eligibility determination. Subjects with the following subtypes of PTCL are eligible, according to 2016 World Health Organization classification prior to the initiation of study drug. Any T-cell lymphoid malignancies not listed below are excluded. Below is the complete list of eligible subtypes: - Enteropathy-associated T-cell lymphoma - Monomorphic epitheliotropic intestinal T-cell lymphoma - Hepatosplenic T-cell lymphoma - Primary cutaneous γδ 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 TFH phenotype - Anaplastic large cell lymphoma, ALK positive - Anaplastic large cell lymphoma, ALK negative\n- Cohort 2 (R/R ATL): Acute, lymphoma, or unfavorable chronic type. R/R ATL should be confirmed by the local pathologist; local diagnosis will be used for eligibility determination. The positivity of anti-HTLV-1 antibody will be locally determined for eligibility\n- Must have at least one of the following lesions which are measurable in 2 perpendicular dimensions on computed tomography (or magnetic resonance imaging) based on local radiological read\n- Documented refractory, relapsed, or progressive disease after at least 1 prior line of systemic therapy. Refractory is defined as - Failure to achieve CR (or uncertified CR [CRu] for ATL) after first-line therapy; or - Failure to reach at least PR or stable disease) after second-line therapy or beyond\n- Must have at least 1 prior line of systemic therapy for PTCL or ATL. - Subjects must also be considered as HCT ineligible during Screening due to disease status (active disease), comorbidities, or other factors; the reason for HCT ineligibility must be clearly documented - In Cohort 1, subjects with ALCL must have prior brentuximab vedotin treatment"}

Exclusion criteria

• {"criterion_text":"- Diagnosis of mycosis fungoides, Sézary syndrome, and primary cutaneous ALCL and systemic dissemination of primary cutaneous ALCL\n- History of treatment with other EZH inhibitors\n- Current use of moderate or strong cytochrome P450 (CYP)3A inducers (Table 10.4)\n- 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\n- Known or suspected hypersensitivity to valemetostat tosylate or any of the excipients\n- 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\n- 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\n- Presence of active central nervous system (CNS) involvement of lymphoma\n- History of autologous HCT within 60 days prior to first dose of study drug\n- History of allogeneic HCT within 90 days prior to the first dose of study drug\n- Clinically significant graft-versus-host disease (GVHD) or GVHD requiring systemic immunosuppressive prophylaxis or treatment\n- 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 or 5 half-lives of the drug, whichever is longer, 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\n- 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 [QTcF] >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 - Subject has clinically relevant bradycardia of ≤ 50 bpm unless the subject 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 graft implantation within 6 months prior to Screening - Uncontrolled angina pectoris within 6 months prior to Screening - New York Heart Association (NYHA) 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 bundle branch block"}

Primary endpoints

• {"endpoint_text":"- Cohort 1 ORR is defined as the proportion of subjects with a BOR of CR or PR, assessed by BICR, among subjects with centrally confirmed PTCL-eligible histology.","definition_or_measurement_approach":"Objective response rate (ORR) measured as proportion with best overall response (BOR) of complete response (CR) or partial response (PR), assessed by blinded independent central review (BICR), among subjects with centrally confirmed PTCL histology."}
• {"endpoint_text":"- Cohort 2 All safety assessments, including AE reporting (TEAEs; TEAESIs; TESAEs; TEAEs by severity [CTCAE grading, including Grade 3 and Grade 4]; fatal events; and TEAEs leading to treatment discontinuation, interruption, or reduction), laboratory assessments, vital signs, and ECG (including QTcF by central ECG reading)","definition_or_measurement_approach":"Comprehensive safety assessment including treatment-emergent adverse events (TEAEs), serious AEs, AESIs, severity grading by CTCAE, laboratory tests, vital signs, and central ECG assessment including QTcF."}

Secondary endpoints

• {"endpoint_text":"- All Cohorts Total and unbound DS-3201a (free form of valemetostat tosylate) and total CALZ-1809a (major metabolite) concentration in plasma","definition_or_measurement_approach":"Pharmacokinetic measurements: plasma concentrations of total and unbound DS-3201a and total CALZ-1809a."}
• {"endpoint_text":"- Cohort 1 only DoR is defined as the time from the date of the first documentation of objective response (CR or PR) to the date of the first documentation of disease progression (progressive orrelapsed disease) based on BICR assessments or to death due to any cause, whichever occurs first.","definition_or_measurement_approach":"Duration of response measured from first documented objective response (CR or PR) to disease progression per BICR or death, whichever occurs first."}
• {"endpoint_text":"- Cohort 1 only CR rate is the percentage of subjects achieving CR as the BOR based onBICR.","definition_or_measurement_approach":"Percentage of subjects with best overall response of complete response as assessed by BICR."}
• {"endpoint_text":"- Cohort 1 only DoCR is defined as the time from the date of the first documentation of CR to the date of the first documentation of disease progression (progressive or relapsed disease) based on BICR assessments or to death due to any cause, whichever occurs first.","definition_or_measurement_approach":"Duration of complete response measured from first documentation of CR to progression per BICR or death."}
• {"endpoint_text":"- Cohort 1 only PR rate is the percentage of subjects achieving PR as the BOR based onBICR assessment.","definition_or_measurement_approach":"Percentage of subjects with best overall response of partial response as assessed by BICR."}
• {"endpoint_text":"- Cohort 1 only All safety assessments, including AE reporting (TEAEs; TEAESIs; TESAEs; TEAEs by severity CTCAE grading, including Grade 3 and Grade 4; fatal events; and TEAEs leading to treatment discontinuation, interruption, or reduction), laboratory assessments, vital signs, and ECG (including QTcF by central ECG reading)","definition_or_measurement_approach":"Safety outcomes using AE reporting, laboratory tests, vital signs and central ECG including QTcF."}
• {"endpoint_text":"- Cohort 1 only PFS is defined as the time interval from the date of the first dose of study drug to the date of disease progression (progressive or relapsed disease) or death due to any cause. Disease progression will be evaluated by investigator assessments","definition_or_measurement_approach":"Progression-free survival measured from first dose to investigator-assessed progression or death."}
• {"endpoint_text":"- Cohort 1 only OS is defined as the time interval from the date of the first dose of study drug to the date of death due to any cause","definition_or_measurement_approach":"Overall survival measured from first dose to death from any cause."}

France

Earliest CTIS Part Ii Submission Date

22-01-2024

Latest Decision Or Authorization Date

08-02-2024

Processing Time Days

17

Number Of Sites

2

Number Of Participants

14

Italy

Earliest CTIS Part Ii Submission Date

22-01-2024

Latest Decision Or Authorization Date

08-02-2024

Processing Time Days

17

Number Of Sites

5

Number Of Participants

23

Spain

Earliest CTIS Part Ii Submission Date

22-01-2024

Latest Decision Or Authorization Date

06-02-2024

Processing Time Days

15

Number Of Sites

1

Number Of Participants

9

Primary sponsor

Full Name

Daiichi Sankyo Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Eresearchtechnology Inc.

Responsibilities

ECG

Name

PPD Global Central Labs

Responsibilities

code: 4

Name

Parexel International (IRL) Limited

Responsibilities

codes: 1,10,12,2,5,6,8,9

Name

Eurofins Central Laboratory B.V.

Responsibilities

Interim Storage of Samples

Name

Perceptive Informatics Inc.

Responsibilities

Medical imaging

Name

Frontage Laboratories Inc.

Responsibilities

code: 4

Third parties

• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"ECG","organisation_type":"Pharmaceutical company"}
• {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"codes: 1,10,12,2,5,6,8,9","organisation_type":"Pharmaceutical company"}
• {"country":"Netherlands","full_name":"Eurofins Central Laboratory B.V.","duties_or_roles":"Interim Storage of Samples","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"Medical imaging","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Frontage Laboratories Inc.","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}