Study of Valemetostat Tosylate Monotherapy in Subjects with Relapsed/Refractory Peripheral T-Cell Lymphoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Daiichi Sankyo Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

3 Nov 2021 → ongoing

Decision date (initial)

2024-02-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

DAIICHI SANKYO, INC.

External identifiers

EU CT number

2023-507381-13-00

EudraCT number

2020-004954-31

ClinicalTrials.gov

NCT04703192

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Cohort 1 only
To estimate the objective response rate (ORR) with valemetostat tosylate monotherapy treatment in R/R PTCL
Cohort 2 Only
To assess the safety and tolerability of valemetostat tosylate
monotherapy

Secondary objectives 6

1. All cohorts To evaluate the pharmacokinetics (PK) of valemetostat and major metabolite (CALZ-1809a)
2. Cohort 1 only To evaluate the duration of response (DoR)
3. Cohort 1 only To assess the CR rate
4. Cohort 1 only To evaluate the duration of CR (DoCR)
5. Cohort 1 only To assess the PR rate
6. Cohort 1 only To assess the safety and tolerability of valemetostat tosylate monotherapy

Conditions and MedDRA coding

Relapsed/Refractory Peripheral T-Cell Lymphoma

Study design 4 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. Written informed consent
2. Subjects ≥18 years of age or the minimum legal adult age (whichever is greater) at the time the ICF is signed.
3. Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0, 1, or 2
4. 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
5. 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
6. 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
7. 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
8. 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 13

1. Diagnosis of mycosis fungoides, Sézary syndrome, and primary cutaneous ALCL and systemic dissemination of primary cutaneous ALCL
2. 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
3. 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
4. Presence of active central nervous system (CNS) involvement of lymphoma
5. History of autologous HCT within 60 days prior to first dose of study drug
6. History of allogeneic HCT within 90 days prior to the first dose of study drug
7. Clinically significant graft-versus-host disease (GVHD) or GVHD requiring systemic immunosuppressive prophylaxis or treatment
8. 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
9. 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
10. History of treatment with other EZH inhibitors
11. Current use of moderate or strong cytochrome P450 (CYP)3A inducers (Table 10.4)
12. 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
13. Known or suspected hypersensitivity to valemetostat tosylate or any of the excipients

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. 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.
2. 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)

Secondary endpoints 8

1. All Cohorts Total and unbound DS-3201a (free form of valemetostat tosylate) and total CALZ-1809a (major metabolite) concentration in plasma
2. 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.
3. Cohort 1 only CR rate is the percentage of subjects achieving CR as the BOR based onBICR.
4. 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.
5. Cohort 1 only PR rate is the percentage of subjects achieving PR as the BOR based onBICR assessment.
6. 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)
7. 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
8. 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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Daiichi Sankyo Inc.

Sponsor organisation

Daiichi Sankyo Inc.

Address

211 Mount Airy Road

City

Basking Ridge

Postcode

07920-2311

Country

United States

Scientific contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Public contact point

Organisation

Daiichi Sankyo Inc.

Contact name

Clinical Trial Office

Third parties 6

Locations

3 EU/EEA countries · 8 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications