Valemetostat Tosylate (DS-3201b), an Enhancer of Zeste Homolog (EZH) 1/2 Dual Inhibitor, for Relapsed/Refractory Peripheral T-Cell Lymphoma (VALENTINE-PTCL01)

NCT04703192 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 3 other identifiers: DS3201-A-U2022020-004954-31jRCT2071200095
• Study Type: interventional
• Target: 155
• Locations: 12 countries
• Sites: 60

Brief Summary

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.

Conditions

Relapsed/Refractory Peripheral T-Cell Lymphoma; Adult T Cell Leukemia/Lymphoma

Keywords

Relapsed/Refractory Peripheral T-Cell Lymphoma; Adult T-Cell Leukemia/Lymphoma; Valemetostat Tosylate; DS-3201b

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Objective Response As Assessed by Blinded Independent Central Review After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)

  For the relapsed/refractory peripheral T-cell lymphoma (PTCL) cohort, objective response rate (ORR) is defined as the proportion of participants with a best overall response (BOR) of complete response (CR) or partial response (PR), assessed by blinded independent central review (BICR), among participants with centrally confirmed PTCL eligible histology.

  From baseline until disease progression or death (whichever occurs first), up to approximately 23 months

• Number of Participants With Treatment-emergent Adverse Events After Administration of Valemetostat Tosylate Monotherapy (Cohort 2)

  Treatment-emergent adverse events (TEAEs) were defined as new AEs or pre-existing conditions that worsen in National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade after the first dose of study drug and up to 30 days after the last dose of study drug.

  From the time the informed consent form is signed up to 30 days after last dose, up to 23 months

Secondary Outcomes (6)

• Plasma Concentrations of DS-3201a and CALZ-1809a After Administration of Valemetostat Tosylate Monotherapy

  Cycle 1 Day 1, 8, 15 Predose; Cycle 1 Day 1 (1, 2, 4, 5 hours Postdose); Cycle 2 Day 1 Predose; Cycle 3 Day 1 to Cycle 5 Day 1 Predose (each cycle is 28 days)

• Duration of Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)

  Time from the date of first documented response (CR or PR) until documented disease progression (progressive or relapsed disease) based on BICR assessments or death from any cause (whichever occurs first), up to approximately 56 months

• Percentage of Participants With Complete Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)

  From baseline to date of first documented objective response of CR, up to approximately 56 months

• Duration of Complete Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)

  Time from the date of first documented CR until documented disease progression (progressive or relapsed disease) based on BICR assessments or death from any cause (whichever occurs first), up to approximately 56 months

• Percentage of Participants With Partial Response After Administration of Valemetostat Tosylate Monotherapy (Cohort 1)

  From baseline to date of first documented objective response of PR, up to approximately 56 months

Study Arms (2)

Cohort 1: Relapsed/Refractory Peripheral T-Cell Lymphoma

EXPERIMENTAL

Participants who will receive 200 mg/day valemetostat tosylate and had an eligible peripheral T-cell lymphoma subtype that was confirmed by independent hematopathology central review.

Drug: Valemetostat Tosylate

Cohort 2: Relapsed/Refractory Adult T-cell Leukemia/Lymphoma

EXPERIMENTAL

Participants who will receive 200 mg/day valemetostat tosylate and had an eligible adult T-cell leukemia/lymphoma subtype that was confirmed by the local pathologist/investigators and by documented positive anti-human T-cell leukemia virus type 1 (HTLV-1) antibody.

Drug: Valemetostat Tosylate

Interventions

Valemetostat Tosylate DRUG

Oral administration of valemetostat tosylate at a dose of 200 mg once daily starting at Cycle 1, Day 1 (continuous for 28-day cycles), until disease progression or unacceptable toxicity

Also known as: DS-3201b

Cohort 1: Relapsed/Refractory Peripheral T-Cell Lymphoma; Cohort 2: Relapsed/Refractory Adult T-cell Leukemia/Lymphoma

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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):
• Diagnosis should be confirmed by the local pathologist; 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 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 T-follicular helper (TFH) phenotype
• Anaplastic large cell lymphoma, ALK positive

You may not qualify if:

• Diagnosis of mycosis fungoides, Sézary syndrome and primary cutaneous ALCL, and systemic dissemination of primary cutaneous ALCL
• Diagnosis of precursor T-cell 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 or 5 half-lives of the drug, whichever is longer, 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

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (60)

City Of Hope National Medical Center

Duarte, California, 91010, United States

Location

Stanford University Medical Center - Cancer Clinical Trials Office - ONCOLOGY

Palo Alto, California, 94304, United States

Location

University of California San Francisco

San Francisco, California, 94143, United States

Location

University Of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Emory University Hospital - Winship Cancer Institute

Atlanta, Georgia, 30322, United States

Location

Northwestern University - Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55901, United States

Location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Hackensack University Medical Center - John Theurer Cancer Center

Hackensack, New Jersey, 07601, United States

Location

Memorial Sloan-Kettering Cancer Center at Memorial Hospital

New York, New York, 10065, United States

Location

Weill Cornell Medicine

New York, New York, 10065, United States

Location

Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

University of Pennsylvania Perelman Center for Advanced Medicine

Philadelphia, Pennsylvania, 19104, United States

Location

Epworth Healthcare

Richmond, 3121, Australia

Location

BC Cancer - Vancouver Centre

Vancouver, British Columbia, V5Z 4E6, Canada

Location

Ottawa Hospital Research Institute

Ottawa, K1H 8L6, Canada

Location

University Health Network Princess Margaret Hospital

Toronto, M5G 1Z5, Canada

Location

CHU de Dijon

Dijon, 21079, France

Location

CHRU de Lille - Hôpital Claude Huriez - Maladies du Sang

Lille, 59037, France

Location

Centre Lyon Berard - Medical Oncology

Lyon, 69008, France

Location

APHP - Hopital Saint Louis

Paris, 75010, France

Location

Hôpital Necker

Paris, 75015, France

Location

Centre Hospitalier Lyon Sud - Hématologie

Pierre-Bénite, 69495, France

Location

Institut Universitaire du Cancer de Toulouse-Oncopole (IUCT-Oncopole)

Toulouse, 31100, France

Location

Universitätsklinikum Halle (Saale) - Klinik und Poliklinik für Innere Medizin IV

Halle, 06120, Germany

Location

ASST Papa Giovanni XXIII - Medicina Trasfusionale ed Ematologia - Bergamo

Bergamo, 24127, Italy

Location

A.O.di Bologna Policl.S.Orsola

Bologna, 40138, Italy

Location

PO San Gerardo, ASST Monza

Monza, 20900, Italy

Location

Fondazione Pascale, IRCCS, Istituto Nazionale dei Tumori

Naples, 80131, Italy

Location

Ospedale S.Maria della Misericordia, AO di Perugia, Università degli Studi di Perugia

Perugia, 06132, Italy

Location

National Hospital Organization Nagoya Medical Center - Hematology

Nagoya, Aichi-ken, 460-0001, Japan

Location

Nagoya City University Hospital

Nagoya, Aichi-ken, 467-8602, Japan

Location

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577, Japan

Location

Hokkaido University Hospital - Medical Oncology Center

Sapporo, Hokkaido, 060-8648, Japan

Location

National Cancer Center Hospital

Chuo Ku, Tokyo, 104-0045, Japan

Location

Kyushu University Hospital

Fukuoka, 812-0054, Japan

Location

Kagoshima University Hospital

Kagoshima, 890-8520, Japan

Location

University Hospital - Kyoto Prefectural University of Medicine

Kyoto, 602-8566, Japan

Location

Nagasaki University Hospital

Nagasaki, 852-8501, Japan

Location

Okayama University Hospital

Okayama, 700-8558, Japan

Location

Leids Universitair Medisch Centrum (LUMC) (Leiden University Medical Center)

Leiden, 2333ZA, Netherlands

Location

Universiteit Maastricht Academisch Ziekenhuis Maastricht

Maastricht, 6229 HX, Netherlands

Location

Severance Hospital, Yonsei University Health System

Seoul, Seoul Teugbyeolsi, 03722, South Korea

Location

Seoul National University Hospital - Department of Internal

Seoul, 03080, South Korea

Location

Asan Medical Center - Oncology

Seoul, 05505, South Korea

Location

Samsung Medical Center - Hematology-Oncology

Seoul, 06351, South Korea

Location

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, 06591, South Korea

Location

ICO Hospital Duran i Reynals

Barcelona, 08029, Spain

Location

Hospital Universitario Vall d'Hebrón

Barcelona, 08035, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, 28040, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, 41013, Spain

Location

Chang Gung Medical Foundation - Kaohsiung Chang Gung Memorial Hospital - Hemato-Oncology

Kaohsiung City, 83301, Taiwan

Location

National Cheng Kung University Hospital - Internal Medicine

Tainan, 70403, Taiwan

Location

National Taiwan University Hospital - Hematology And Oncology

Taipei, 10002, Taiwan

Location

Chang Gung Medical Foundation - LinKou Chang Gung Memorial Hospital - Hematology and Oncology - Hematology and Oncology

Taoyuan, 33305, Taiwan

Location

University College London Hospital

London, NW1 2PG, United Kingdom

Location

Nottingham City Hospital - Clinical Haematology

Nottingham, NG5 1PB, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

Related Publications (1)

• Zinzani PL, Izutsu K, Mehta-Shah N, Barta SK, Ishitsuka K, Cordoba R, Kusumoto S, Bachy E, Cwynarski K, Gritti G, Prica A, Jacobsen E, Feldman T, Guillermin Y, Ennishi D, Yoon DH, Domenech ED, Zain J, Wang J, Kim JS, Poel MV, Jin J, Wu S, Chen Y, Moriyama T, Inoue A, Nakajima K, Horwitz SM. Valemetostat for patients with relapsed or refractory peripheral T-cell lymphoma (VALENTINE-PTCL01): a multicentre, open-label, single-arm, phase 2 study. Lancet Oncol. 2024 Dec;25(12):1602-1613. doi: 10.1016/S1470-2045(24)00503-5. Epub 2024 Oct 29.

  PMID: 39486433 DERIVED

MeSH Terms

Conditions

Lymphoma, T-Cell, Peripheral; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Leukemia; Hematologic Diseases

Results Point of Contact

• Title: Contact for Clinical Trial Information
• Organization: Daiichi Sanyko, Inc

CTRinfo@dsi.com

908-992-6400

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 7, 2021
• First Posted: January 11, 2021
• Study Start: June 3, 2021
• Primary Completion: May 10, 2023
• Study Completion (Estimated): February 19, 2027
• Last Updated: December 9, 2025
• Results First Posted: July 22, 2024

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

GB (3); ES (5); CA (3); JP (10); DE (1); TW (4); IT (5); KR (5); AU (1); FR (7); NL (2); US (14)