RELAPSE/REFRACTORY B-CELL LYMPHOMA MedDRA version: 21.0 Level: PT Classification code 10003902 Term: B-cell lymphoma recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: PT Classification code 10003903 Term: B-cell lymphoma refractory System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: Valemetostat Tosylate
Product Code: DS-3201b
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Valemetostat tosilate
Current Sponsor code: DS-3201b
Other descriptive name: Va
Sponsors
LYSARC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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 rerrangement, 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 2. 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): 4a. 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 or 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 4b. For FL, MZL and other indolent 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. 4c. For MCL: 2 prior lines including at least one immunochemotherapy and one BTK inhibitor. 4d. 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 8. Adequ
Exclusion criteria
Exclusion criteria: 1. Participant with prior exposure to EZH2 inhibitor 2. Participant with active lymphomatous involvement of the central nervous system (CNS) at screening 3. 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. 4. Major surgery within 4 weeks before the first dose of study drug. 5. 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 6. Subjects currently taking medications that are known moderate or strong CYP3A inducers (refer to Appendix 7 for a list of example drugs) o 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 7. Vaccinated with live, attenuated vaccines within 6 months of enrollment (except COVID vaccine) 8. 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, 9. History of CAR T-cells therapy within 30 days prior to the first dose of study drug 10. History of autologous or allogeneic HCT within 90 days prior to the first dose of study drug 11. 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). 12. 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 13. 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). 14. Positive serology of human immunodeficiency virus (HIV) 15. Participant with prolongation of corrected QT interval using Fridericia's formula (QTcF) to > 470 milliseconds (msec) (obtained on average of 3 ECGs) 16. Participant with venous thrombosis or pulmonary embolism not treated 17. Participant with complications of hepatic cirrhosis, interstitial pneumonia, or pulmonary fibrosis 18. Participant with active infection requiring systemic therapy 19. Woman who are pregnant (positive serum pregnancy test at screening) or breastfeeding 20. Participant who were deemed as inappropriate to participate in the study by the investigator or sub-investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate efficacy of valemetostat tosylate (DS-3201b) monotherapy in relapsed/refractory B cell lymphoma patients within 6 distinct cohorts: -Cohort 1: 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 rerrangement, transformed indolent lymphoma and grade 3b follicular lymphoma) (with at least 8 EZH2 mutant) -Cohort 2: Follicular Lymphoma (grade 1, 2, 3a) EZH2 wild-type -Cohort 2bis: Follicular Lymphoma (grade 1, 2, 3a) EZH2 mutant (gain of function mutations) -Cohort 3: Mantle Cell Lymphoma (MCL) -Cohort 4: Marginal Zone Lymphoma (MZL) and others indolent lymphoma (Waldenström macroglobulinemia) -Cohort 5: Hodgkin Lymphoma (HL);Secondary Objective: -Rate of complete response (CR) -Progression-free survival (PFS) -Duration of response (DOR) -Time to response (TTR) -Safety - To evaluate the plasma pharmacokinetics of valemetostat tosylate (DS-3201b) and major metabolite (CALZ-1809a).;Primary end point(s): Primary endpoint will be the overall response rate (ORR) defined as the proportion of subjects achieving best overall response of partial response (PR) or complete response (CR) at any time, according to the Lugano 2014 classification (PET-CT–Based Response for FDG-avid lymphomas or CT-Based Response if not) and determined by investigator. ;Timepoint(s) of evaluation of this end point: For each cohort, the primary endpoint analysis will be performed when the number of evaluable patients requested has received at least 12 cycles of study treatment, have died, have withdrawn their consent, have stopped treatment or are lost to follow up (whatever the event that occurs first). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Rate of complete response (CR) - Progression-free survival (PFS) - Duration of response (DOR) - Time to response (TTR) - Safety - To evaluate the plasma pharmacokinetics of valemetostat tosylate (DS-3201b) and major metabolite (CALZ-1809a).;Timepoint(s) of evaluation of this end point: The final analysis (secondary endpoints) will be performed when all patients received at least 12 cycles of study treatment, have died, have withdrawn their consent, or are lost to follow up (whatever the event that occurs first). | — |
Countries
Belgium, France
Contacts
Public ContactProject Manager
LYSARC
Outcome results
None listed