Relapsed or Refractory Mature T- and NK-cell Neoplasms MedDRA version: 20.0 Level: HLGT Classification code 10025321 Term: Lymphomas non-Hodgkin's T-cell System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Product Name: Tislelizumab
Pharmaceutical Form: Concentrate for solution for injection/infusion
INN or Proposed INN: Tislelizumab
CAS Number: 1858168-59-8
Current Sponsor code: BGB-A317
Concentration
Sponsors
BeiGene, Ltd. c/o BeiGene USA, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Histologically confirmed diagnosis of relapsed or refractory, mature Tcell and NK-cell neoplasms based on the WHO 2016 classification of tumors of hematopoietic and lymphoid tissue. Patients will be allocated to three cohorts based on their histologic diagnosis: • Cohort 1: Extranodal NK/T-cell lymphoma (nasal or non-nasal type) ? Patients with aggressive NK leukemia are excluded • Cohort 2: Other mature T-cell neoplasms, limited to the following histologies: ? Peripheral T-cell lymphoma - not otherwise specified (PTCL-NOS) ? Angioimmunoblastic T-cell lymphoma (AITL) ? Anaplastic large cell lymphoma (ALCL) • Cohort 3: Stage IB-IVB cutaneous T-cell lymphomas, limited to the following histologies: ? Mycosis fungoides (MF) ? Sèzary syndrome (SS) 2. Male or female = 18 years of age at the time of informed consent (or acceptable age according to local regulations, whichever is older) 3. Previously received 1 or more appropriate systemic therapies (e.g. non-anthracycline based regimens such as L-asparaginase-based therapy) for cohort 1 or combination chemotherapy (e.g. CHOP, EPOCH, or similar therapy) for cohort 2. Radiation therapy alone would not be acceptable as previous therapy • For patients with relapsed or refractory anaplastic large cell lymphoma regardless of anaplastic lymphoma kinase (ALK) status, must have received prior therapy with brentuximab vedotin (applicable only to countries where brentuximab vedotin received marketing approval) 4. Disease progression during or after completion of most recent therapy or refractory disease. Refractory disease is defined as failure to achieve CR or PR to most recent therapy, and most recent therapy was an appropriate systemic therapy for mature T-cell or NK-cell lymphoma 5. For cohorts 1 and 2, patients must have lesions that are measurable by imaging, where measurable is defined as = 1 lesion that is > 1.5 cm for nodal lesions and > 1 cm for extranodal lesions. For cohort 3, patients are not required to have measurable disease by imaging. 6. Availability of either unstained tissue (block or unstained slides) or stained slides, and pathology report for central confirmation of mature T-cell or NK-cell lymphoma. If stained slides or unstained tissue (block or unstained slides) are not available or are insufficient, a fresh tumor tissue sample is mandatory for central pathology. Central pathology confirmation is not required prior to enrollment. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 (see table 3 in protocol). 8. Has life expectancy = 6 months. 9. Patients must have forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) > 60% by pulmonary function test (PFT), carbon monoxide diffusion capacity (DLCO) > 60% predicted value, and FEV1 and FVC > 50% predicted value; all PFTs must be obtained within 4 weeks prior to the first dose of tislelizumab. 10. Adequate organ function defined as: • Absolute neutrophil count (ANC) > 1000/mm3(without growth factor support within 7 days of ANC measurement) • Platelet > 50000/mm3(without growth factor support or transfusion within 7 days of platelets measurement) • Hemoglobin > 80 g/L (prior transfusion is acceptable) • Creatinine clearance = 30 ml/min (as estimated by the CockcroftGault equation or as measured by nuclear medicine scan or 24-hour urine collection) (see Appendix 9 of protocol) • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase,
Exclusion criteria
Exclusion criteria: 1. Known central nervous system involvement by leukemia or lymphoma 2. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 agent 3. Meets one of the following scenarios for hematopoietic stem cell transplantation and/or chimeric antigen receptor T cell (CAR-T) therapy: • Is eligible for autologous or allogeneic stem cell transplantation, unless patient has refused transplantation • Has undergone prior allogeneic hematopoietic stem cell transplantation or organ transplantation • Has received autologous stem cell transplantation within 6 months prior to first dose of study drug • Has received CAR-T therapy within 12 months prior to first dose of study drug 4. Has received: • Systemic chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks (or 5 half-lives, whichever is shorter) prior to study Day 1 • Recent treatment with another monoclonal antibody within 4 weeks prior to study Day 1 • Investigational treatment or device within 4 weeks (or 5 half-lives, whichever is shorter) prior to study Day 1 • For cohort 3 patients, phototherapy within 2 weeks or any topical therapy within 1 week prior to study Day 1 •Or has not recovered from AEs (ie, = Grade 1 or baseline level) due to prior therapy 5. Concurrent or prior malignancy within the past 3 years, except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, carcinoma in situ of the cervix or breast, or localized Gleason score 6 or lower prostate cancer 6. Active autoimmune diseases or history of autoimmune diseases that may relapse (see Appendix 3) Note: Patients with the following diseases are not excluded and may proceed to further screening: a. Type I diabetes under control b. Hypothyroidism (provided it is managed with hormone replacement therapy only) c. Controlled celiac disease d. Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, alopecia) except when such diseases significantly interfere with response assessment of patients in cohort 3 e. Any other disease that is not expected to recur in the absence of external triggering factors 7. Has known history of interstitial lung disease, non-infectious pneumonitis, pulmonary fibrosis, acute lung diseases or evidence of dyspnea at rest or pulse oximetry of 10 mg daily of prednisone or equivalent) or other immunosuppressive medication within 14 days before study drug administration. Note: Patients who are currently or have previously been on any of the following steroid regimens are not excluded: a. Adrenal replacement steroid (dose = 10 mg daily of prednisone or equivalent) b. Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with minimal systemic absorption except when given for treatment of MF or SS c. Short course (= 7 days) of corticosteroid prescribed prophylactically (eg, for contrast dye allergy) or for the treatment of a non-autoimmune condition (eg, delayed-type hypersensitivity reaction caused by contact allergen 9. Has a known active TB (Bacillus Tuberculosis) infection 10. Known infection with HIV, human T-cell lymphotropic virus (HTLV)-1, -2, or serologic status reflecting active hepatitis B or C infection as follows: • Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb). Patients with pr
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate efficacy of tislelizumab in patients Relapsed or Refractory Mature T- and NK-cell Neoplasms as measured by overall response rate and determined by investigator. • For cohorts 1 and 2, overall response rate will be measured using the Lugano criteria (Cheson et al 2014) with Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) modification for immunomodulatory drugs (Cheson et al 2016). • For cohort 3, overall response rate will be measured using the International Society for Cutaneous Lymphomas/European Organization of Research and Treatment of Cancer (ISCL/EORTC) guidelines (Olsen et al 2011). ;Secondary Objective: For cohorts 1 and 2, efficacy measures will be determined using the Lugano criteria (Cheson et al 2014) with LYRIC modification for immunomodulatory drugs (Cheson et al 2016). For cohort 3, efficacy measures will be determined using the ISCL/EORTC guidelines (Olsen et al 2011). • To evaluate the efficacy of tislelizumab, as determined by the investigator and measured by the following: - Duration of response for all cohorts - Progression-free survival for all cohorts - Overall survival for cohorts 1 and 2 - Rate of complete response or complete metabolic response for all cohorts - Time to response for all cohorts - Patient-reported outcomes (EQ-5D-5L and EORTC QLQ-C30) for all cohorts • To evaluate safety and tolerability of tislelizumab for all cohorts;Timepoint(s) of evaluation of this end point: Efficacy will be assessed every 12 weeks for 96 weeks, then every 24 weeks for an additional 96 weeks, and then yearly until disease progression. ;Primary end point(s): The primary endpoint is overall response rate as determined by investigator. Overall response rate is defined as the proportion of patients achieving a best overall response of complete response or partial response. Efficacy will be assessed every 12 weeks for 96 weeks, then every 24 weeks for an additional 96 weeks, and then yearly un | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • For cohorts 1 and 2, efficacy measures will be determined using the Lugano criteria (Cheson et al 2014) with LYRIC modification for immunomodulatory drugs (Cheson et al 2016). For cohort 3, efficacy measures will be determined using the ISCL/EORTC guidelines (Olsen et al 2011). All measures will be assessed by the investigator. • Duration of response defined as the time from the first determination of an objective response until progression or death, whichever occurs first, for all cohorts • Progression-free survival defined as the time from first study drug administration to the date of disease progression or death, whichever occurs first, for all cohorts • Overall survival, defined as the time from first study drug administration to the date of death due to any reason, for cohorts 1 and 2 • Rate of complete response or complete metabolic response defined as the proportion of patients who achieve complete response or complete metabolic response as best overall response, for all cohorts • Time to response defined as the time from first study drug administration to the time the response criteria (complete response or partial response) are first met, for all cohorts • Patient-reported outcomes measured by EORTC QLQ-C30 and EQ-5D-5L questionnaires for all cohorts • Safety parameters, including AEs, SAEs, clinical laboratory tests, physical exams, and vital signs for all cohorts ;Timepoint(s) of evaluation of this end point: A) Duration of response until progression or death, whichever occurs first, for all cohorts B) Progression-free survival at selected timepoints, for all cohorts C) Overall Survival (OS) at selected timepoints, for cohorts 1 and 2 D) Rate of complete response or complete metabolic response, for all cohorts E) Time-to-response at selected timepoints, for all cohorts F) The EORTC QLQ-C30 and EQ-5D-5L questionnaires will be summarized for each assessment timepoint, for all cohorts G) Safety and Pharmacokineti | — |
Countries
Canada, China, France, Germany, Hong Kong, Italy, Taiwan, United States
Contacts
Public ContactBeiGene Clinical Support
BeiGene, Ltd.
Outcome results
None listed