Study of Valemetostat Tosylate as a Single Agent in Patients With Relapse/Refractory B-cell Lymphoma

NCT04842877 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: VALYM
• Study Type: interventional
• Target: 141
• Locations: 2 countries
• Sites: 22

Brief Summary

This is a multicenter, prospective, single arm, non-randomized, open-label, phase 2 clinical study to evaluate safety and efficacy of valemetostat tosylate (DS-3201b) in patients with relapsed or refractory B cell lymphoma with 6 cohorts of patients including 2 biology-driven cohorts. Up to 141 patients will be enrolled in 6 different cohorts (40 patients with aggressive B-cell lymphoma, 41 with follicular lymphoma (FL), 20 with Mantle Cell Lymphoma (MCL) and 20 with other indolent lymphomas, and 20 patients with Hodgkin lymphoma (HL)). FL patients with EZH2 mutant (gain of function mutations) will be enrolled in the cohort 2bis. At least 8 aggressive B-cell lymphoma patients with EZH2 mutant will be enrolled in the cohort 1. The primary endpoint is the overall response rate (ORR) determined by investigator assessment.

Conditions

Lymphoma, B-Cell

Keywords

relapse; valemetostat tosylate

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate (ORR)

  ORR according to Lugano Response Criteria (2014)

  when mature response rate data have been observed, estimated as no later than 12 months after the last patient in each cohort has received the first dose of study drug

Secondary Outcomes (16)

• Complete Response Rate (CRR)

  After 3 cycles of treatment (each cycle of 28 days, id est (ie) 3 months)

• Complete Response (CR) Rate

  After 6 cycles of treatment (each cycle of 28 days, id est (ie) 6 months)

• Complete Response (CR) Rate

  After 9 cycles of treatment (each cycle of 28 days, id est (ie) 9 months)

• Complete Response (CR) Rate

  After 12 cycles of treatment (each cycle of 28 days, id est (ie) 12 months)

• Progression-Free Survival (PFS)

  After 12 cycles(each cycle is 28 days) of study treatment for the last patient included (estimated 3 years of study)

Study Arms (1)

Experimental arm

EXPERIMENTAL

Experimental arm: Valemetostat tosylate (DS-3201b) is given continuously at 200 mg QD.

Drug: Valemetostat tosylate

Interventions

Valemetostat tosylate DRUG

200mg QD continuously until disease progression, consent withdrawal, unacceptable drug-related toxicity, lost to follow-up, major protocol deviation, pregnancy, termination by sponsor or death, whichever occurs first.

Also known as: DS-3201b

Experimental arm

Eligibility Criteria

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

You may qualify if:

• Participants with confirmed histological diagnosis of B-cell non-Hodgkin's lymphoma of aggressive B-cell lymphoma (diffuse large B-cell lymphoma-not otherwise specified, primary mediastinal B-cell lymphoma, high grade B-cell lymphoma-not otherwise specified and high grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangement, transformed indolent lymphoma and grade 3b follicular lymphoma), FL (grade 1, 2, 3a), MCL, MZL or other indolent lymphoma (Waldenström macroglobulinemia), or HL according to the World Health Organization (WHO) 2016 classification of hematopoietic and lymphoid tissue.
• \. Participant who had progressive disease (PD) or did not have a response (CR or PR) in previous systemic therapy, or relapsed or progressed after previous systemic therapy 3. Participant who has measurable disease by the Lugano criteria (ie longest diameter of a nodal site \> 1.5cm and/or longest diameter of an extranodal site \> 1.0 cm) 4. Participant who had previous standard therapy with at least: (note: patients having received prior CAR-T therapy can be enrolled):
• For aggressive B-cell lymphoma : 1 prior line of therapy (in transformed indolent lymphoma patient must have received at least one line of treatment containing an anthracycline-based regimen before of after transformation) containing an anti-CD20 antibody and an anthracycline (unless anthracycline-based therapy is contraindicated) and if patient is considered unable to benefit from intensification treatment with autologous stem cell transplant (ASCT) as defined by at least one of the following criteria:
• Relapsed following, or refractory to, previous ASCT
• Ineligible for intensification treatment due to age or significant comorbidity
• Ineligible for intensification treatment due to failure to mobilize an acceptable number of hematopoietic stem cells
• Refused intensification treatment and/or ASCT
• For FL, MZL and other indolent non-Hodgkin's lymphoma (NHL): 2 prior lines of systemic therapy with at least one anti-CD20 monoclonal antibody. Local involved field radiotherapy for limited stage disease is not considered as a previous line. Subjects with prior ASCT may be included. Note: for Splenic Marginal Zone Lymphoma (SMZL), splenectomy is considered as one line; for Extranodal Marginal Zone Lymphoma (ENMZL), Helicobacter pylori eradication is not considered as a previous line.
• For MCL: 2 prior lines including at least one immunochemotherapy and one BTK inhibitor.
• For HL: 3 prior lines including at least one line with anthracycline-based chemotherapy (unless anthracycline-based therapy is contraindicated), one line containing brentuximab-vedotin and one line containing an anti-PD1 or anti-PDL1 antibody and must be considered unable to benefit from intensification treatment with autologous stem cell transplant (ASCT) as defined by at least one of the following criteria:
• Relapsed following, or refractory to, previous ASCT
• Did not achieve at least a partial response to a standard salvage regimen
• Ineligible for intensification treatment due to age or significant comorbidity
• Ineligible for intensification treatment due to failure to mobilize an acceptable number of hematopoietic stem cells
• Refused intensification treatment and/or ASCT 5. Participant with Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 6. Adequate renal function defined as calculated creatinine clearance ≥ 40 mL/min per the Cockcroft and Gault formula 7. Adequate bone marrow function:

You may not qualify if:

• Participant with prior exposure to EZH2 inhibitor
• Participant with active lymphomatous involvement of the central nervous system (CNS) at screening
• Any prior treatment-related (ie, chemotherapy, immunotherapy, radiotherapy), clinically significant toxicities have not resolved to ≤ Grade 1 per CTCAE version 5.0, or prior treatment-related toxicities are clinically unstable and clinically significant at time of enrollment.
• Major surgery within 4 weeks before the first dose of study drug.
• Inability to take oral medication, or malabsorption syndrome or any other uncontrolled gastrointestinal condition (eg, nausea, diarrhea, or vomiting) that might impair the bioavailability of the drug
• Subjects currently taking medications that are known moderate or strong CYP3A inducers
• If currently used, these medications need to be discontinued at least 14 days prior to study drug administration; replacement by alternative medications that are not moderate or strong CYP3A inducers can be considered according to medical need
• Vaccinated with live, attenuated vaccines within 6 months of enrollment (except COVID vaccine)
• Use of any standard or experimental anti-cancer drug therapy within 4 weeks or a minimum of 3 half lives of the drug, whatever the shortest prior to first administration of study drug,
• History of CAR T-cells therapy within 30 days prior to the first dose of study drug
• History of autologous or allogeneic hematopoietic cell transplantation (HCT) within 90 days prior to the first dose of study drug
• Patients taking corticosteroids within 2 weeks prior to first administration of study drug, unless administered at a cumulated dose equivalent of prednisone to ≤ 10mg /day (within these 2 weeks).
• Participant with significant cardiovascular impairment: history of congestive heart failure greater than New York Heart Association (NYHA) Class II, uncontrolled arterial hypertension, unstable angina, myocardial infarction, or stroke within 6 months of the first dose of study drug; or cardiac ventricular arrhythmia
• Subjects with malignancies other than B cell lymphomas except subjects who have been disease-free for 2 years (subjects with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible).
• Positive serology of human immunodeficiency virus (HIV)

Sponsors & Collaborators

• The Lymphoma Academic Research Organisation: lead
• Daiichi Sankyo: collaborator

Study Sites (22)

A.Z. Sint Jan AV

Bruges, 8000, Belgium

Location

University Hospital Gent

Ghent, 9000, Belgium

Location

CH Tourelle Peltzer

Verviers, 4800, Belgium

Location

CHU Mont-Godinne

Yvoir, Belgium

Location

CH d'Avignon

Avignon, 84000, France

Location

CH de la Côte Basque

Bayonne, 64109, France

Location

Institut Bergonié

Bordeaux, 33076, France

Location

Institut d'Hématologie de Basse Normandie

Caen, 14076, France

Location

Ch Metropole Savoie - Site Chambery

Chambéry, 73000, France

Location

CHU d'Estaing

Clermont-Ferrand, 63000, France

Location

François Lemonnier

Créteil, 94010, France

Location

CHU de Dijon

Dijon, 21034, France

Location

Chd de Vendee

La Roche-sur-Yon, 85925, France

Location

Clinique Victor Hugo

Le Mans, 72000, France

Location

Service des Maladies du Sang - CHRU de Lille

Lille, 59037, France

Location

Institut Paoli Calmette

Marseille, 13273, France

Location

CHU de Montpellier

Montpellier, 34295, France

Location

Gh Region Mulhouse Et Sud Alsace

Mulhouse, 68070, France

Location

CHU Hôtel Dieu

Nantes, 44093, France

Location

Emmanuel Bachy

Pierre-Bénite, 69495, France

Location

CHU Pontchaillou

Rennes, 35003, France

Location

Ch de Bretagne Atlantique -

Vannes, 56017, France

Location

MeSH Terms

Conditions

Lymphoma, B-Cell; Recurrence

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Franck Morschhauser, PhD

  Lymphoma Study Association

  STUDY CHAIR

• Emmanuel Bachy, PhD

  Lymphoma Study Association

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a multicenter, prospective, single arm, non-randomized, open-label, phase 2 clinical study

Study Record Dates

• First Submitted: April 7, 2021
• First Posted: April 13, 2021
• Study Start: June 11, 2021
• Primary Completion: December 3, 2024
• Study Completion (Estimated): October 1, 2026
• Last Updated: February 19, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (18); BE (4)