TAZEMETOSTAT for Relapsed/refractory follicular lymphoma

Stratification factors

• EZH2 mutation status (WT vs MT)

Inclusion criteria

• {"criterion_text":"- Have voluntarily agreed to provide written informed consent and demonstrated willingness and ability to comply with all aspects of the protocol."}
• {"criterion_text":"- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2."}
• {"criterion_text":"- Have provided sufficient tumor tissue block or unstained slides for EZH2 mutation testing in all subjects to allow for stratification a. If EZH2 mutation status is known from site-specific testing, subjects can be enrolled. Tumor tissue will be required for confirmatory testing of EZH2 status at study-specific laboratories. If the archival tumor sample was collected more than 24 months prior to the anticipated administration of the first dose (cycle 1 day 1), then a fresh biopsy must be provided. Fresh tumor biopsy is appropriate except for procedures deemed to result in unacceptable risk because of the anatomical location including brain, lung/mediastinum, pancreas, or endoscopic procedures extending beyond the esophagus, stomach, or bowel. Archival tumor biopsy sections mounted on slides are also acceptable. NOTE: Confirmatory testing will also be performed for Stage 1, if local EZH2 testing is conducted, unless there is insufficient tumor tissue to perform testing after discussion with the Sponsor’s or Designee Medical Monitor."}
• {"criterion_text":"- Time between prior anticancer therapy and first dose of tazemetostat as follows: a. Cytotoxic chemotherapy – At least 21 days. b. Noncytotoxic chemotherapy (eg, small molecule inhibitor) – At least 14 days. c. Nitrosoureas – At least 6 weeks. d. Monoclonal and/or bispecific antibodies or CAR T – At least 28 days. e. Radiotherapy – At least 6 weeks from prior radioisotope therapy; at least 12 weeks from 50% pelvic or total body irradiation."}
• {"criterion_text":"- Adequate renal function defined as calculated creatinine clearance ≥30 mL/minute per the Cockcroft and Gault formula."}
• {"criterion_text":"- Adequate bone marrow function: a. Absolute neutrophil count (ANC) ≥1000/mm3 (≥1.0 × 10^9/L) if no lymphoma infiltration of bone marrow OR ANC ≥750/mm3 (≥75 × 10^9/ L) with bone marrow infiltration • Without growth factor support (filgrastim or pegfilgrastim) for at least 14 days. b. Platelets ≥75,000/mm3 (≥75 × 10^9/L) • Evaluated at least 7 days after last platelet transfusion. c. Hemoglobin ≥9.0 g/dL • May receive transfusion"}
• {"criterion_text":"- Adequate liver function: a. Total bilirubin ≤1.5 × the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia of Gilbert’s syndrome. b. Alkaline phosphatase (ALP) (in the absence of bone disease), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) ≤3 × ULN (≤5 × ULN if subject has liver infilration)."}
• {"criterion_text":"- International normalized ratio (INR) ≤1.5 × ULN and activated partial thromboplastin time (aPTT) ≤1.5 × ULN (unless on warfarin, then INR ≤3.0). In subjects with thromboembolism risk, prophylactic anticoagulation, or antiplatelet therapy at investigator discretion is recommended."}
• {"criterion_text":"- Females of childbearing potential (FCBP) must have a negative urine or serum pregnancy tests (beta-human chorionic gonadotropin [β-hCG] tests with a minimum sensitivity of 25 mIU/mL or equivalent units of β-hCG) at screening within 10 to 14 days prior to first dose of study drug. The subject may not receive study drug until the study doctor has verified that the results of pregnancy tests are negative. All females will be considered to be of childbearing potential unless they are naturally postmenopausal (at least 24 months consecutively amenorrhoeic [amenorrhea following cancer therapy does not rule out childbearing potential] and without other known or suspected cause) or have been sterilized surgically (ie, total hysterectomy and/or bilateral oophorectomy, with surgery completed at least 1 month before dosing)."}
• {"criterion_text":"- Females of childbearing potential (FCBP) enrolled must either practice complete abstinence or agree to use two reliable methods of contraception simultaneously. This includes ONE highly effective method of contraception and ONE additional effective contraceptive method. Contraception must begin at least 28 days prior to first dose of study drug, continue during study treatment (including during dose interruptions), and for 12 months after study drug discontinuation. Female subjects must also refrain from breastfeeding for 12 months following last dose of study drug. If the below contraception methods are not appropriate for the FCBP, she must be referred to a qualified contraception provider to determine the medically effective contraception method appropriate for the subject. The following are examples of highly effective and additional effective methods of contraception: Examples of highly effective methods: • Intrauterine device (IUD) • Hormonal (ovulation inhibitory combined [estrogen and progesterone] birth control pills or intravaginal/transdermal system, injections, implants, levonorgestrel-releasing intrauterine system [IUS], medroxyprogesterone acetate depot injections, ovulation inhibitory progesterone-only pills [e.g. desogestrel]) NOTE: There is a potential for tazemetostat interference with hormonal contraception methods due to enzymatic induction. • Bilateral tubal ligation • Partner’s vasectomy (if medically confirmed [azoospermia] and sole sexual partner). Examples of additional effective methods: • Male latex or synthetic condom, • Diaphragm, • Cervical Cap NOTE: Female subjects of childbearing potential exempt from these contraception requirements are subjects who practice complete abstinence from heterosexual sexual contact. True abstinence is acceptable when this is in line with the preferred and usual lifestyle of the subject. Periodic abstinence (eg, calendar, ovulation, symptothermal, or post ovulation methods) and withdrawal are not acceptable methods of contraception."}
• {"criterion_text":"- All study participants enrolled must be registered into the applicable pregnancy prevention program (e.g. REVLIMID REMS in the US, Pregnancy Prevention Programme [PPP] in Europe) for lenalidomide to be administered and be willing and able to comply with the requirements of the applicable program as appropriate for the country in which the drug is being used. a. Female subjects of childbearing potential (FCBP) must adhere to the scheduled pregnancy testing as required in the applicable pregnancy prevention program. During study treatment, FCBP must agree to have pregnancy testing weekly for the first 28 days of study participation and then every 28 days for FCBP with regular or no menstrual cycles OR every 14 days for FCBP with irregular menstrual cycles. FCBP must also have a pregnancy test at end of lenalidomide treatment, at day 14 (for FCBP with irregular menstrual cycles) and day 28 following the last dose of lenalidomide and at overall treatment discontinuation (at the End-of-Treatment/30-day safety Follow-up visit). Female subjects exempt from this requirement are subjects who have been naturally postmenopausal for at least 24 consecutive months OR are surgically sterilized (ie, total hysterectomy or bilateral oophorectomy) with surgery at least 1 month before the first dose of study treatment."}
• {"criterion_text":"- Within 7 days prior to randomization, all clinically significant toxicity related to a prior anticancer treatment (ie, chemotherapy, immunotherapy, and/or radiotherapy must have either resolved to Grade 1 per NCI CTCAE Version 5.0 OR are clinically stable and no longer clinically significant."}
• {"criterion_text":"- Male subjects must either practice complete abstinence or agree to use a latex or synthetic condom, even with a successful vasectomy (medically confirmed azoospermia), during sexual contact with a pregnant female or FCBP from first dose of study drug, during study treatment (including during dose interruptions), and for 3 months after study drug discontinuation. NOTE: Male subjects must not donate semen or sperm from first dose of study drug, during study treatment (including during dose interruptions), and for 3 months after study drug discontinuation."}
• {"criterion_text":"- Males or females are ≥18 years of age, or per country adult legal age regulations, at the time of providing voluntary written informed consent."}
• {"criterion_text":"- Life expectancy ≥3 months before enrollment."}
• {"criterion_text":"- Meet requirements for hepatitis and human immunodeficiency virus (HIV) infection as follows: • Negative serologic or polymerase chain reaction (PCR) test results for acute or chronic hepatitis B virus (HBV) infection Note: Participants whose HBV infection status could not be determined by serologic test results have to be negative for HBV-DNA by PCR to be eligible for study participation. Participants seropositive for HBV with undetectable HBV DNA by PCR are permitted with appropriate antiviral prophylaxis. • Negative test results for hepatitis C virus (HCV) Note: Participants who are positive for HCV antibody must be negative for HCV RNA by PCR to be eligible for study participation • If HIV positive, HIV infection is controlled. Based on Cancer Clinical Trial Eligibility Criteria: Patients with HIV, Hepatitis B Virus, or Hepatitis C Virus Infections - Guidance for Industry (https://www.fda.gov/media/121319/download), patients with HIV should be considered eligible if they have CD4+ T-cell counts ≥ 350 cells/uL and in general, if they have not had an opportunistic infection within the past 12 months. Other exclusion criteria should be considered regarding the drug-drug interaction if antiviral drugs are used. Therefore, in case of controlled HIV infection, since antiviral drugs are used, trial patients should be on established ART for at least 4 weeks and have an HIV viral load less than 400 copies/mL prior to enrolment."}
• {"criterion_text":"- Have histologically confirmed FL, Grades 1 to 3A."}
• {"criterion_text":"- Must have been previously treated with at least 1 prior systemic chemotherapy, immunotherapy, or chemoimmunotherapy: a. Systemic therapy includes treatments such as: i. Rituximab monotherapy ii. Chemotherapy given with or without rituximab iii. Radioimmunoconjugates such as 90Y-ibritumomab tiuxetan and 131I- tositumomab. b. Systemic therapy does not include, for example: i. Local involved field radiotherapy for limited-stage disease ii. Helicobacter pylori eradication c. Prior investigational therapies will be allowed provided the subject has received at least 1 prior systemic therapy as discussed in Inclusion Criterion #6a. d. Prior autologous/allogeneic hematopoietic stem cell transplant (HSCT) will be allowed. e. Prior chimeric antigen receptor T-cell therapy (CAR T) will be allowed."}
• {"criterion_text":"- Must have documented relapsed, refractory, or PD after treatment with systemic therapy (refractory defined as less than PR or disease progression <6 months after last dose)."}
• {"criterion_text":"- Have measurable disease as defined by the Lugano Classification (Cheson, 2014; Appendix 5)."}

Exclusion criteria

• {"criterion_text":"- Prior exposure to tazemetostat or other inhibitor(s) of EZH2."}
• {"criterion_text":"- Major surgery within 4 weeks before the first dose of study drug. a. Note: Minor surgery (eg, minor biopsy of extracranial site, central venous catheter placement, shunt revision) is permitted within 3 weeks prior to enrollment."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Prolongation of corrected QT interval using Fridericia’s formula (QTcF) to ≥480 msec at screening or history of long QT syndrome."}
• {"criterion_text":"- Venous thrombosis or pulmonary embolism within the last 3 months before starting tazemetostat. a. Note: Participants who have experienced deep vein thrombosis/ pulmonary embolism more than 3 months before enrollment are eligible but are recommended to receive prophylaxis"}
• {"criterion_text":"- Have an active infection requiring systemic therapy."}
• {"criterion_text":"- Known hypersensitivity to any component of tazemetostat or lenalidomide; known severe hypersensitivity to any component of rituximab requiring hospitalization or resuscitation."}
• {"criterion_text":"- Active viral infection with or seropositive for HBV: HBV surface antigen (HBsAg) positive OR HBsAg negative, anti-HBs positive and/or anti-HBc positive with detectable HBV DNA. NOTE: Subjects who are HBsAg negative, anti-HBs positive and/or anti-HBc positive, but with undetectable viral DNA and normal ALT are eligible. Subjects who are seropositive due to HBV vaccination (HBsAg negative, HBV surface antibody [anti-HBs] positive, and HBV core antibody [anti-HBc] negative) are eligible."}
• {"criterion_text":"- Active viral infection with hepatitis C virus (as measured by positive HCV antibody and detectable viral RNA, HIV), or known active infection with human T-cell lymphotropic virus. NOTE: Subjects with a history of hepatitis C infection (HCV antibody reactive) who have normal ALT and undetectable HCV RNA are eligible."}
• {"criterion_text":"- Any other medical or social condition that, in the Investigator’s judgment, will interfere with a participant’s ability to provide informed consent, to receive study drugs, or meet study demands, or that substantially increases the risk associated with the subject’s participation in the study, or that may interfere with interpretation of results."}
• {"criterion_text":"- Female subjects who are pregnant or lactating/breastfeeding."}
• {"criterion_text":"- Are unable to take oral medication OR have malabsorption syndrome or any other uncontrolled gastrointestinal condition (eg, nausea, diarrhea, vomiting) that might impair the bioavailability of tazemetostat."}
• {"criterion_text":"- Subjects who have undergone a solid organ transplant."}
• {"criterion_text":"- Subjects with malignancies other than FL. a. Exception: Subjects with another malignancy who have been disease-free for 3 years, or subjects with a history of a completely resected non-melanoma skin cancer or successfully treated in situ carcinoma are eligible."}
• {"criterion_text":"- Prior exposure to lenalidomide or drugs of the same class."}
• {"criterion_text":"- Grade 3b, mixed histology, or FL that has histologically transformed to diffuse large B-cell lymphoma (DLBCL) (subjects transformed from DLBCL to FL may be enrolled)."}
• {"criterion_text":"- Has thrombocytopenia, neutropenia, or anemia of Grade ≥3 (per CTCAE Version 5.0 criteria) or any prior history of myeloid malignancies, including myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or myeloproliferative neoplasm (MPN)."}
• {"criterion_text":"- Has a prior history of T-cell lymphoblastic lymphoma (T-LBL)/T-cell acute lymphoblastic leukemia (T-ALL) or B-cell acute lymphoblastic leukemia (B-ALL)."}
• {"criterion_text":"- Subjects with uncontrolled leptomeningeal metastases or brain metastases or history of previously treated brain metastases."}
• {"criterion_text":"- Subjects taking medications that are known strong CYP3A inhibitors and strong or moderate CYP3A inducers (including St. John’s wort)."}
• {"criterion_text":"- Are unwilling to exclude grapefruit juice, Seville oranges, and grapefruits from the diet and/or consumed within 1 week of the first dose of study drug and for the duration of the study."}

Primary endpoints

• {"endpoint_text":"- Recommended Phase 3 Dose (RP3D) of tazemetostat in combination with rituximab and lenalidomide (R2) The safety and tolerability of tazemetostat in combination with R2 in subjects with R/R FL will be evaluated. RP3D of tazemetostat for further evaluation in phase 3 will be selected as assessed by the occurrence of treatment-emergent dose-limiting toxicities (DLTs) and adverse events (AEs).","definition_or_measurement_approach":"Selection of RP3D based on occurrence of treatment-emergent dose-limiting toxicities (DLTs) and adverse events (AEs) observed during Phase 1b safety run-in (Stage 1). Safety and tolerability assessments are used to choose the recommended Phase 3 dose."}
• {"endpoint_text":"- Progression-Free Survival (PFS) in the Intent-to-treat wild-type (ITT-WT) population PFS is defined as the time from the date of randomization to the time of confirmed disease progression per the 2014 Lugano Classification or death, whichever occurs first, as assessed by Investigators.","definition_or_measurement_approach":"PFS defined as time from randomization to confirmed disease progression per 2014 Lugano Classification or death, whichever occurs first; assessed by Investigators (and also evaluated by blinded IRC in specified analyses)."}
• {"endpoint_text":"- PFS in the Intent-to-treat mutant-type (ITT-MT) population PFS is defined as the time from the date of randomization to the time of confirmed disease progression per the 2014 Lugano Classification or death, whichever occurs first, as assessed by Investigators.","definition_or_measurement_approach":"PFS defined as time from randomization to confirmed disease progression per 2014 Lugano Classification or death, whichever occurs first; assessed by Investigators (and also evaluated by blinded IRC in specified analyses)."}

Secondary endpoints

• {"endpoint_text":"- Phase 1: Pharmacokinetics (PK) of tazemetostat: Maximum (peak) Observed Plasma Drug Concentration (Cmax). Cmax will be recorded from the PK blood samples collected.","definition_or_measurement_approach":"Cmax measured from PK blood samples collected per PK sampling schedule."}
• {"endpoint_text":"- Phase 1: PK of tazemetostat, EPZ 6930 (desethyl metabolite), and lenalidomide as data permit: Time to Maximum Observed Drug Concentration (Tmax)","definition_or_measurement_approach":"Tmax determined from PK concentration-time profiles for tazemetostat, metabolite EPZ 6930, and lenalidomide."}
• {"endpoint_text":"- Phase 1: PK of tazemetostat: area under the plasma concentration-time curve (AUC) from time 0 to the time of the last quantifiable concentration [AUC(0-t)]","definition_or_measurement_approach":"AUC(0-t) calculated from PK concentration-time data."}
• {"endpoint_text":"- Phase 1: PK of tazemetostat: area under the plasma concentration-time curve (AUC) from time 0 to infinity [AUC(0-∞)]","definition_or_measurement_approach":"AUC(0-∞) estimated from PK data and terminal elimination parameters."}
• {"endpoint_text":"- Phase 1: The apparent terminal elimination half-life (t1/2) of tazemetostat, EPZ 6930 (desethyl metabolite), and lenalidomide as data permit","definition_or_measurement_approach":"t1/2 derived from terminal phase of PK concentration-time profile."}
• {"endpoint_text":"- Complete Response Rate (CRR) in ITT-WT population CRR is defined as the proportion of participants achieving CR according to the 2014 Lugano Classification, as assessed by the Investigator and a blinded Independent Review Committee (IRC).","definition_or_measurement_approach":"CRR = proportion achieving complete response per 2014 Lugano Classification; assessed by Investigator and blinded IRC."}
• {"endpoint_text":"- CRR in ITT-MT population CRR is defined as the proportion of participants achieving CR according to the 2014 Lugano Classification, as assessed by the Investigator and a blinded IRC","definition_or_measurement_approach":"CRR per 2014 Lugano Classification in ITT-MT; assessed by Investigator and blinded IRC."}
• {"endpoint_text":"- CRR in the Relapsed/Refractory (R/R) Follicular Lymphoma (FL) population regardless of mutation status CRR is defined as the proportion of participants achieving CR according to the 2014 Lugano Classification, as assessed by the Investigator and a blinded IRC.","definition_or_measurement_approach":"CRR per Lugano (2014) assessed by Investigator and blinded IRC in overall R/R FL population."}
• {"endpoint_text":"- Objective Response Rate (ORR) in the ITT-WT population ORR is defined as the proportion of participants achieving a best overall response (BOR) of partial response (PR) or complete response (CR) according to the 2014 Lugano Classification, as assessed by the Investigator and a blinded IRC.","definition_or_measurement_approach":"ORR = proportion with BOR of PR or CR per Lugano (2014); assessed by Investigator and blinded IRC."}
• {"endpoint_text":"- ORR in the ITT-MT population ORR is defined as the proportion of participants achieving a best overall response (BOR) of partial response (PR) or complete response (CR) according to the 2014 Lugano Classification, as assessed by the Investigator and a blinded IRC.","definition_or_measurement_approach":"ORR (ITT-MT) per Lugano (2014); assessed by Investigator and blinded IRC."}
• {"endpoint_text":"- ORR in the R/R FL population regardless of mutation status ORR is defined as the proportion of participants achieving a best overall response (BOR) of partial response (PR) or complete response (CR) according to the 2014 Lugano Classification, as assessed by the Investigator and a blinded IRC","definition_or_measurement_approach":"ORR in overall R/R FL per Lugano (2014); assessed by Investigator and blinded IRC."}
• {"endpoint_text":"- Overall Survival (OS) in the ITT-WT population OS is defined as the time from the date of randomization until death due to any cause.","definition_or_measurement_approach":"OS measured from randomization to death from any cause."}
• {"endpoint_text":"- OS in the ITT-MT populatio","definition_or_measurement_approach":"OS in ITT-MT measured from randomization to death from any cause."}
• {"endpoint_text":"- OS in the R/R FL population regardless of mutation status","definition_or_measurement_approach":"OS in overall R/R FL measured from randomization to death from any cause."}
• {"endpoint_text":"- PFS in the ITT-WT population, assessed by a blinded IRC","definition_or_measurement_approach":"PFS per Lugano (2014) assessed by blinded Independent Review Committee."}
• {"endpoint_text":"- PFS in the ITT-MT population, assessed by a blinded IRC","definition_or_measurement_approach":"PFS per Lugano (2014) assessed by blinded IRC in ITT-MT."}
• {"endpoint_text":"- PFS in the R/R FL population regardless of mutation status, assessed by a blinded IRC","definition_or_measurement_approach":"PFS per Lugano (2014) assessed by blinded IRC in overall R/R FL."}
• {"endpoint_text":"- PFS in the R/R FL population regardless of mutation status, assessed by the Investigator","definition_or_measurement_approach":"Investigator-assessed PFS per Lugano (2014) in overall R/R FL."}
• {"endpoint_text":"- Duration Of Response (DOR) in the ITT-WT population DOR is defined as the time from initial CR or PR to documented progression or death due to any cause, whichever occurs first, for those participants with a CR or PR, as assessed by the Investigator and by a blinded IRC","definition_or_measurement_approach":"DOR measured from initial CR/PR to progression or death; assessed by Investigator and blinded IRC."}
• {"endpoint_text":"- DOR in the ITT-MT population DOR is defined as the time from initial CR or PR to documented progression or death due to any cause, whichever occurs first, for those participants with a CR or PR, as assessed by the Investigator and by a blinded IRC","definition_or_measurement_approach":"DOR (ITT-MT) from CR/PR to progression or death; assessed by Investigator and blinded IRC."}
• {"endpoint_text":"- DOR in the R/R FL population regardless of mutation status DOR is defined as the time from initial CR or PR to documented progression or death due to any cause, whicheve","definition_or_measurement_approach":"DOR in overall R/R FL from initial CR/PR to progression or death; assessed by Investigator and blinded IRC."}
• {"endpoint_text":"- Duration Of Complete Response (DOCR) in the ITT-WT population DOCR is defined as the time from initial CR to documented progression or death due to any cause, whichever occurs first, for those participants with CR, assessed by the Investigator and by a blinded IRC.","definition_or_measurement_approach":"DOCR measured from initial CR to progression or death; assessed by Investigator and blinded IRC."}
• {"endpoint_text":"- DOCR in the ITT-MT population DOCR is defined as the time from initial CR to documented progression or death due to any cause, whichever occurs first, for those participants with CR, assessed by the Investigator and by a blinded IRC.","definition_or_measurement_approach":"DOCR (ITT-MT) from initial CR to progression or death; assessed by Investigator and blinded IRC."}
• {"endpoint_text":"- DOCR in the R/R FL population regardless of mutation status DOCR is defined as the time from initial CR to documented progression or death due to any cause, whichever occurs first, for those participants with CR, assessed by the Investigator and by a blinded IRC.","definition_or_measurement_approach":"DOCR in overall R/R FL from initial CR to progression or death; assessed by Investigator and blinded IRC."}
• {"endpoint_text":"- Disease Control Rate (DCR) in the ITT-WT population DCR, defined as the proportion of participants with best overall response of CR, PR, or stable disease (SD) lasting 12 or more months, as assessed by the Investigator and by a blinded IRC.","definition_or_measurement_approach":"DCR = proportion with BOR of CR, PR, or SD lasting ≥12 months; assessed by Investigator and blinded IRC."}
• {"endpoint_text":"- DCR in the ITT-MT population DCR, defined as the proportion of participants with best overall response of CR, PR, or stable disease (SD) lasting 12 or more months, as assessed by the Investigator and by a blinded IRC.","definition_or_measurement_approach":"DCR (ITT-MT) per same definition; assessed by Investigator and blinded IRC."}
• {"endpoint_text":"- DCR in the R/R FL population regardless of mutation status DCR, defined as the proportion of participants with best overall response of CR, PR, or stable disease (SD) lasting 12 or more months, as assessed by the Investigator and by a blinded IRC.","definition_or_measurement_approach":"DCR in overall R/R FL per same definition; assessed by Investigator and blinded IRC."}
• {"endpoint_text":"- Population PK parameters of oral clearance (CL/F) of tazemetostat","definition_or_measurement_approach":"Population PK modeling to estimate CL/F for tazemetostat."}
• {"endpoint_text":"- Population PK parameters of oral volume of distribution (Vd/F) of tazemetostat.","definition_or_measurement_approach":"Population PK modeling to estimate Vd/F for tazemetostat."}
• {"endpoint_text":"- Population PK parameters of first-order absorption rate constant (Ka) for tazemetostat.","definition_or_measurement_approach":"Population PK modeling to estimate Ka for tazemetostat."}
• {"endpoint_text":"- Percentage of Participants Experiencing Adverse Events (AEs) An Adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.","definition_or_measurement_approach":"Proportion of participants experiencing AEs; AEs graded per NCI CTCAE v5.0."}
• {"endpoint_text":"- Percentage of Participants with Clinically Significant Changes in Physical Examination Percentage of participants with clinically significant changes in physical examination findings will be reported. The clinical significance will be graded by the investigator according to the National Cancer Institute Common Terminology Criteria for AEs (CTCAE) Version 5.0.","definition_or_measurement_approach":"Proportion with clinically significant physical exam changes graded per NCI CTCAE v5.0."}
• {"endpoint_text":"- Percentage of Participants with Clinically Significant Changes in Vital Signs Percentage of participants with clinically significant changes in vital signs findings will be reported. The clinical significance will be graded by the investigator according to the National Cancer Institute Common Terminology Criteria for AEs (CTCAE) Version 5.0.","definition_or_measurement_approach":"Proportion with clinically significant vital sign changes graded per NCI CTCAE v5.0."}
• {"endpoint_text":"- Percentage of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Readings Percentage of participants with clinically significant changes in ECG Readings will be reported. The clinical significance will be graded by the investigator according to the National Cancer Institute Common Terminology Criteria for AEs (CTCAE) Version 5.0.","definition_or_measurement_approach":"Proportion with clinically significant ECG changes graded per NCI CTCAE v5.0."}
• {"endpoint_text":"- Performance status evaluated by Eastern Cooperation Oncology Group (ECOG) ECOG is a 6-point performance status scale used to assess performance using PA as a key indicator (e.g., 0 = fully active, 2 = up and about more than 50% of walking hours, 5 = dead) Performance status will be assessed per usual clinical practice and will be recorded in the medical record.","definition_or_measurement_approach":"ECOG performance status assessed per clinical practice and recorded; used as safety/functional endpoint."}
• {"endpoint_text":"- Duration of Study Drug Exposure Duration of exposure to study drug will be reported","definition_or_measurement_approach":"Duration on study drug recorded for each participant (treatment exposure duration)."}
• {"endpoint_text":"- Percentage of study drug taken by participants","definition_or_measurement_approach":"Adherence measured as percentage of study drug doses taken."}
• {"endpoint_text":"- Quality of life questionnaires evaluation Evaluate and compare health-related quality of life as measured by the EuroQOL 5-Dimension 5-Level (EQ-5D-5L) instrument and the Functional Assessment of Cancer Therapy –Lymphoma (FACT-Lym)","definition_or_measurement_approach":"QoL measured by EQ-5D-5L and FACT-Lym instruments; scores compared between arms/populations per statistical analysis plan."}

Belgium

Earliest CTIS Part Ii Submission Date

07-06-2024

Latest Decision Or Authorization Date

28-11-2024

Processing Time Days

174

Number Of Sites

1

Number Of Participants

10

Hungary

Earliest CTIS Part Ii Submission Date

07-06-2024

Latest Decision Or Authorization Date

20-02-2026

Processing Time Days

623

Number Of Sites

4

Number Of Participants

12

France

Earliest CTIS Part Ii Submission Date

07-06-2024

Latest Decision Or Authorization Date

22-02-2026

Processing Time Days

625

Number Of Sites

22

Number Of Participants

70

Germany

Earliest CTIS Part Ii Submission Date

07-06-2024

Latest Decision Or Authorization Date

18-02-2026

Processing Time Days

621

Number Of Sites

9

Number Of Participants

14

Italy

Earliest CTIS Part Ii Submission Date

07-06-2024

Latest Decision Or Authorization Date

20-02-2026

Processing Time Days

623

Number Of Sites

19

Number Of Participants

50

Poland

Earliest CTIS Part Ii Submission Date

07-06-2024

Latest Decision Or Authorization Date

22-02-2026

Processing Time Days

625

Number Of Sites

7

Number Of Participants

38

Spain

Earliest CTIS Part Ii Submission Date

07-06-2024

Latest Decision Or Authorization Date

18-02-2026

Processing Time Days

621

Number Of Sites

12

Number Of Participants

32

Primary sponsor

Full Name

Epizyme Inc.

Organisation Type

Pharmaceutical company

Country Of Registered Address

United States

Contract research organisations

Name

Parexel International (IRL) Limited

Responsibilities

Sponsor duties codes: 1,12,2,3,6,7 (roles per sponsor duties listing in CTIS record)

Name

Q2 Solutions LLC

Responsibilities

Laboratory/clinical trial testing services (sponsor duties code: 4)

Name

Eurofins Central Laboratory B.V.

Responsibilities

Central laboratory services (sponsor duties code: 4)

Name

Perceptive Informatics Inc.

Responsibilities

Data/informatics services (sponsor duties code: 13)

Third parties

• {"country":"Ireland","full_name":"Parexel International (IRL) Limited","duties_or_roles":"codes: 1,12,2,3,6,7","organisation_type":"Pharmaceutical company / CRO"}
• {"country":"United States","full_name":"Q2 Solutions LLC","duties_or_roles":"codes: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Netherlands","full_name":"Eurofins Central Laboratory B.V.","duties_or_roles":"codes: 4","organisation_type":"Pharmaceutical company / central laboratory"}
• {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"codes: 13","organisation_type":"Pharmaceutical company / data services"}