Follicular Lymphoma, Refractory Follicular Lymphoma, Relapsed/Refractory Follicular Lymphoma
Conditions
Keywords
Epizyme, Tazverik, Tazemetostat (EPZ-6438), Lenalidomide, Revlimid, Rituximab, Rituxan, Follicular lymphoma, EZH2
Brief summary
The participants of this study would have relapsed/refractory follicular lymphoma. Follicular lymphoma is a type of blood cancer. It is referred to as 'relapsed' when the disease has come back after a period of improvement after that follows a treatment regimen and 'refractory' when treatment no longer works. Stage 1 of this trial studied the safety and the level that adverse effects of each of the study drug combinations can be tolerated (known as tolerability). It is also designed to establish a recommended study drug dosage for stage 2 and 3. Stage 1 of the study is completed. Stages 2 and 3 were designed to evaluate and compare how long participants live without their disease getting worse when receiving the study drug in combination with other drug treatment versus the placebo (dummy drug) in combination with other drug treatment. However, following an urgent safety measure, treatment with tazemetostat and placebo was discontinued, enrollment was stopped, and the study was unblinded. As a result, post-urgent safety measure analyses are descriptive in nature.
Detailed description
In Stage 2, participants were enrolled into study cohorts based on whether they have a specific genetic mutation in the EZH2 gene. All participants received treatment in 28-day cycles. After 12 cycles, they continued with maintenance treatment using either the study drug or placebo, depending on their original treatment group. However, following the urgent safety measure, treatment was permanently discontinued and no further interventional procedures are being conducted. The study included participants with and without the mutation in EZH2 gene. Enrollment was to be completed separately for each group. In China, some participants also had extra blood tests to better understand how the drug behaves in the body; no further pharmacokinetic data are being collected following the urgent safety measure. Stage 3 focuses on long-term safety monitoring after the urgent safety measure. Participants treated with tazemetostat will be followed for up to 5 years after the last dose of tazemetostat
Interventions
DRUGTazemetostat
Stage 1 (Phase 1b): Tazemetostat was escalated from a starting dose of 400 mg orally twice daily to 600 mg orally twice daily to 800 mg PO twice daily in 28-day cycles as tolerated in a standard 3 + 3 design. Tazemetostat will be administered as monotherapy at an 800 mg twice daily dose for up to 2 years after the initial 12 months of combination therapy. Following implementation of the urgent safety measure, tazemetostat administration was discontinued. No further dosing is performed.
DRUGPlacebo oral tablet
Stage 2: Placebo administered orally twice daily in continuous 28-day cycles. Placebo will be administered as monotherapy twice daily dose for up to 2 years after the initial 12 months of combination therapy. Following implementation of the urgent safety measure, placebo administration was discontinued.
COMBINATION_PRODUCTLenalidomide
Lenalidomide 20 mg capsules or 10 mg capsules (if creatinine clearance ≥60 mL/minute or \<60 mL/minute), administered PO QD on days 1 to 21 for 12 cycles.
COMBINATION_PRODUCTRituximab
Rituximab 375 mg/m2 IV on days 1, 8, 15, and 22 of cycle 1; then on day 1 of cycles 2 to 5.
Sponsors
Epizyme, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Stage 1: Open-Label (Phase 1b: Safety run-in): All participants received Tazemetostat in combination with Lenalidomide and Rituximab Stage 2: Double-blinded (Phase 3): * Study drug arm: Tazemetostat in combination with Lenalidomide and Rituximab * Placebo arm: Placebo in combination with Lenalidomide and Rituximab Stage 3: Long-term Follow-up of participants in Stage 1/2 after treatment with tazemetostat for long-term safety monitoring
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Have voluntarily agreed to provide written informed consent and demonstrated willingness and ability to comply with all aspects of the protocol. 2. Males or females are ≥18 years of age, or per country adult legal age regulations, at the time of providing voluntary written informed consent. 3. Life expectancy ≥3 months before enrollment. 4. Meet requirement 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. 5. Have histologically confirmed FL, Grades 1 to 3A. 6. 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. 7. 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). 8. Have measurable disease as defined by the Lugano Classification (Cheson, 2014; Appendix 5). 9. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. 10. 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. 11. 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. 12. Time between prior anticancer therapy and first dose of tazemetostat as follows: 1. Cytotoxic chemotherapy - At least 21 days. 2. Noncytotoxic chemotherapy (eg, small molecule inhibitor) - At least 14 days. 3. Nitrosoureas - At least 6 weeks. 4. Monoclonal and/or bispecific antibodies or CAR T - At least 28 days. 5. Radiotherapy - At least 6 weeks from prior radioisotope therapy; at least 12 weeks from 50% pelvic or total body irradiation. 13. Adequate renal function defined as calculated creatinine clearance ≥30 mL/minute per the Cockcroft and Gault formula. 14. 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 15. Adequate liver function: 1. Total bilirubin ≤1.5 × the upper limit of normal (ULN) except for unconjugated hyperbilirubinemia of Gilbert's syndrome. 2. 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). 16. 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. 17. 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). 18. 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. 19. 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 theapplicable 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. 20. 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b: Recommended Phase 3 Dose (RP3D) of tazemetostat in combination with rituximab and lenalidomide (R2) | Subjects are evaluated for DLTs during the first 28-day cycle. The RP3D for Phase 3 was selected at the end of Stage 1 | The safety and tolerability of tazemetostat in combination with R2 in subjects with R/R FL were evaluated. RP3D of tazemetostat for further evaluation in phase 3 was selected as assessed by the occurrence of treatment-emergent dose-limiting toxicities (DLTs) and adverse events (AEs). |
| Phase 3: Progression-Free Survival (PFS) in the Intent-to-treat wild-type (ITT-WT) populations | Stage 2: Up to 72 months | 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. PFS will be assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further efficacy data are collected, and any post-urgent safety measure analyses are descriptive in nature. |
| Phase 3: PFS in the Intent-to-treat mutant-type (ITT-MT) population | Stage 2: Up to 72 months | 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. |
| Phase 3: PFS in the R/R FL population regardless of mutation status by Investigator assessment | Stage 2: Up to 72 months | PFS is defined as the time from the date of randomization to the first observation of documented objective disease progression per the 2014 Lugano Classification or death due to any cause, whichever occurs first. 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. |
| Phase 3: Progression-Free Survival (PFS) in the all comer (ITT-All) populations. | Stage 2: Up to 72 months | 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. PFS will be assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further efficacy data are collected, and any post-urgent safety measure analyses are descriptive in nature. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1b: Pharmacokinetics (PK) of tazemetostat: Maximum (peak) Observed Plasma Drug Concentration (Cmax). | Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle) | Cmax will be recorded from the PK blood samples collected. |
| Phase 1b: PK of tazemetostat, EPZ 6930 (desethyl metabolite), and lenalidomide as data permit: Time to Maximum Observed Drug Concentration (Tmax) | Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle) | — |
| Phase 1b: 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)], | Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle) | — |
| Phase 1b: PK of tazemetostat: area under the plasma concentration-time curve (AUC) from time 0 to infinity [AUC(0-∞)] | Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle) | — |
| Phase 1b: The apparent terminal elimination half-life (t1/2) of tazemetostat, EPZ 6930 (desethyl metabolite), and lenalidomide as data permit | Stage 1: In cycles 1 and 2 on days 1 and 15 (28 days cycle) | — |
| Phase 3: Complete Response Rate (CRR) in ITT-WT population | Stage 2: Up to 96 months | 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). CRR is assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further response assessments are performed, and analyses are descriptive in nature. |
| Phase 3: CRR in ITT-MT population | Stage 2: Up to 96 months | 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. CRR is assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further response assessments are performed, and analyses are descriptive in nature. |
| Phase 3: CRR in the Relapsed/Refractory (R/R) Follicular Lymphoma (FL) population regardless of mutation status | Stage 2: Up to 96 months | 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. CRR is assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further response assessments are performed, and analyses are descriptive in nature. |
| Phase 3: Objective Response Rate (ORR) in the ITT-WT population | Stage 2: Up to 96 months | 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. ORR is assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further response assessments are performed, and analyses are descriptive in nature. |
| Phase 3: ORR in the ITT-MT population | Stage 2: Up to 96 months | 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. ORR is assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further response assessments are performed, and analyses are descriptive in nature. |
| Phase 3: ORR in the R/R FL population regardless of mutation status | Stage 2: Up to 96 months | 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. ORR is assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further response assessments are performed, and analyses are descriptive in nature. |
| Phase 3: Overall Survival (OS) in the ITT-WT population | Stage 2: Up to 96 months | OS is defined as the time from the date of randomization until death due to any cause. |
| Phase 3: OS in the ITT-MT population | Stage 2: Up to 96 months | — |
| Phase 3: OS in the R/R FL population regardless of mutation status | Stage 2: Up to 96 months | — |
| Phase 3: PFS in the ITT-WT population, assessed by a blinded IRC | Stage 2: Up to 96 months | — |
| Phase 3: PFS in the ITT-MT population, assessed by a blinded IRC | Stage 2: Up to 96 months | — |
| Phase 3: PFS in the R/R FL population regardless of mutation status, assessed by a blinded IRC | Stage 2: Up to 96 months | — |
| Phase 3: Duration Of Response (DOR) in the ITT-WT population | Stage 2: Up to 96 months | 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. DOR is assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further response assessments are performed, and analyses are descriptive in nature. |
| Phase 3: DOR in the ITT-MT population | Stage 2: Up to 96 months | 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. DOR is assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further response assessments are performed, and analyses are descriptive in nature. |
| Phase 3: DOR in the R/R FL population regardless of mutation status | Stage 2: Up to 96 months | 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. DOR is assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further response assessments are performed, and analyses are descriptive in nature. |
| Phase 3: Disease Control Rate (DCR) in the ITT-WT population | Stage 2: Up to 96 months | 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. DCR is assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further response assessments are performed, and analyses are descriptive in nature. |
| Phase 3: DCR in the ITT-MT population | Stage 2: Up to 96 months | 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. DCR is assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further response assessments are performed, and analyses are descriptive in nature. |
| Phase 3: DCR in the R/R FL population regardless of mutation status | Stage 2: Up to 96 months | 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. DCR is assessed based on data collected prior to treatment discontinuation as a result of the urgent safety measure. Following implementation of the urgent safety measure, no further response assessments are performed, and analyses are descriptive in nature. |
| PK parameters will be summarized by plasma concentrations of tazemetostat and lenalidomide descriptively. | Stage 2: In cycles 2, 4, 6, and 12 at Day 1 (28 days cycle) | PK assessments will be conducted on samples collected until the urgent safety measure. No further PK analyses are performed post-urgent safety measure. |
| Percentage of Participants Experiencing Adverse Events (AEs) | Up to 36 months | 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. |
| Percentage of Participants with Clinically Significant Changes in Physical Examination | Up to 36 months | 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. |
| Percentage of Participants with Clinically Significant Changes in Vital Signs | Up to 36 months | 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. |
| Percentage of Participants with Clinically Significant Changes in Electrocardiogram (ECG) Readings | Up to 72 months | 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. |
| Performance status evaluated by Eastern Cooperation Oncology Group (ECOG) | Up to 72 months | 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. |
| Duration of Study Drug Exposure | Up to 36 months | Study drug exposure reflects administration prior to implementation of the urgent safety measure. No further investigational drug exposure occurs post-urgent safety measure. |
Countries
Australia, Belgium, Brazil, Canada, China, France, Germany, Hungary, Italy, Poland, Singapore, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORIpsen Medical Director
Ipsen
Outcome results
None listed