Study of BGB-A317 in Participants With Relapsed or Refractory Mature T- and NK-cell Neoplasms

Study Overview
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Brief Summary
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This was a multi-center, prospective, non-randomized, open-label, Phase 2 clinical study to evaluate the safety and efficacy of BGB-A317 in participants with relapsed or refractory mature T- and natural killer (NK)-cell neoplasms. There were three cohorts: Cohort 1: Relapsed or refractory (R/R) extranodal NK/T cell lymphoma (ENKTL; nasal or non-nasal type) Cohort 2: Other R/R mature T-cell neoplasms, limited to the following histologies: peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), or anaplastic large-cell lymphoma (ALCL) Cohort 3: R/R cutaneous T-cell lymphoma, limited to mycosis fungoides (MF) or Sèzary syndrome (SS) Study procedures included a Screening phase (up to 35 days); Treatment phase (until disease progression, intolerable toxicity, or withdrawal of informed consent, whichever occurs first); Safety Follow-up phase (up to 90 days following last study treatment for all adverse events (AEs) and serious adverse events (SAEs)); and Survival follow-up phase (duration varying by participant).

Official Title
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A Phase 2, Open-Label Study of BGB-A317 in Patients With Relapsed or Refractory Mature T- and NK-cell Neoplasms

Conditions
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Extranodal NK/T-cell Lymphoma, Extranodal NK/T-cell Lymphoma, Nasal Type, Extranodal NK T Cell Lymphoma, Adult Nasal Type Extranodal NK/T-cell Lymphoma, Extranodal NK T Cell Lymphoma, Nasal, Peripheral T Cell Lymphoma, PTCL, Angioimmunoblastic T-cell Lymphoma, Angioimmunoblastic T-Cell Lymphoma Recurrent, Angioimmunoblastic T-Cell Lymphoma Refractory, Peripheral T-cell Lymphoma NOS, Peripheral T-Cell Lymphoma, Not Otherwise Specified, Peripheral T-Cell Lymphoma Refractory, Anaplastic Large Cell Lymphoma, Anaplastic Large Cell Lymphoma, ALK-Positive, Anaplastic Large Cell Lymphoma, ALK-negative, ALK-negative Anaplastic Large Cell Lymphoma, ALK-Positive Anaplastic Large Cell Lymphoma, Cutaneous T-cell Lymphoma

Intervention / Treatment
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* Drug: Tislelizumab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria Confirmed diagnosis of relapsed or refractory extranodal NK/T-cell lymphoma (nasal or non-nasal type, peripheral T-cell lymphoma - not otherwise specified, angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, mycosis fungoides, or Sezary syndrome) Age 18 years or older Relapsed or refractory to at least 1 prior systemic therapy Measurable disease by computed tomography (CT)/magnetic resonance imaging (MRI) for participants in Cohort 1 and 2 Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2 Life expectancy ≥ 6 months Adequate respiratory function Adequate bone marrow function Adequate renal and hepatic function Key Exclusion Criteria Known central nervous system (CNS) involvement by lymphoma Previously received immune checkpoint therapy 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 Active autoimmune disease or history of autoimmune diseases that may relapse with some exceptions Severe or debilitating pulmonary disease Clinically significant cardiovascular disease Active fungal, bacterial, and/or viral infection requiring systemic therapy Known infection with HIV or active viral hepatitis B or C infection Major surgery within 4 weeks of the first dose of study drug Pregnant or lactating women Vaccination with a live vaccine within 35 days prior to the first dose of study drug Hypersensitivity to tislelizumab Concurrent participation in another therapeutic clinical trial NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: ENKTL<br>Participants with relapsed or refractory (R/R) extranodal natural killer-/T-cell lymphoma (ENKTL; nasal or non-nasal type) were treated with tislelizumab 200 mg intravenously (IV) on Day 1 of each cycle until disease progression, intolerable toxicity, or treatment discontinuation for any other reason (21 days per cycle) | Drug: Tislelizumab<br>* Administered intravenously<br>* Other names: BGB-A317;|
| Experimental: Cohort 2: PTCL-NOS, AITL, and ALCL<br>Participants with other R/R mature T-cell neoplasms [limited to peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic large-cell lymphoma (ALCL)] were treated with tislelizumab 200 mg intravenously (IV) on Day 1 of each cycle until disease progression, intolerable toxicity, or treatment discontinuation for any other reason (21 days per cycle) | Drug: Tislelizumab<br>* Administered intravenously<br>* Other names: BGB-A317;|
| Experimental: Cohort 3: MF and SS<br>Participants with R/R cutaneous T-cell lymphoma [limited to mycosis fungoides (MF) and Sèzary syndrome (SS)] were treated with tislelizumab 200 mg intravenously (IV) on Day 1 of each cycle until disease progression, intolerable toxicity, or treatment discontinuation for any other reason (21 days per cycle) | Drug: Tislelizumab<br>* Administered intravenously<br>* Other names: BGB-A317;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) | ORR is defined as the percentage of participants achieving a best overall response of complete response or partial response as determined by the investigator using Lugano criteria with Lymphoma Response to Immunomodulatory Therapy Criteria (LYRIC) modification for cohorts 1 and 2 and International Society for Cutaneous Lymphomas/European Organization of Research and Treatment of Cancer (ISCL/EORTC) guidelines for cohort 3. | Up to approximately 3 years and 1 week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) | DOR defined as the time from the first determination of an objective response until progression or death, whichever occurs first, as assessed by the investigator using Lugano criteria with LYRIC modification for cohorts 1 and 2 and ISCL/EORTC guidelines for cohort 3. | Up to approximately 3 years and 1 week | 
| Progression-free Survival (PFS) | PFS is defined as the time from first study drug administration to the date of disease progression or death, whichever occurs first, as assessed by the investigator using Lugano criteria with LYRIC modification for cohorts 1 and 2 and ISCL/EORTC guidelines for cohort 3. | Up to approximately 3 years and 1 week | 
| Overall Survival (OS) | OS defined as the time from first study drug administration to the date of death due to any reason for cohorts 1 and 2. | Up to approximately 3 years and 1 week | 
| Complete Response Rate (CRR) | CRR is defined as the percentage of participants who achieve complete response or complete metabolic response as best overall response as assessed by the investigator using Lugano criteria with LYRIC modification for cohorts 1 and 2 and ISCL/EORTC guidelines for cohort 3. | Up to approximately 3 years and 1 week | 
| Time to Response (TTR) | 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 as assessed by the investigator using Lugano criteria with LYRIC modification for cohorts 1 and 2 and ISCL/EORTC guidelines for cohort 3. | Up to approximately 3 years and 1 week | 
| Quality of Life Assessment: EQ-5D-5L Change From Baseline in Visual Analogue Score | Mean change from baseline at safety follow-up visit in EQ-5D-5L visual analogue score (VAS). The EQ-5D-5L measures health outcomes using a VAS to record a participant's self-rated health on a scale from 0 to 100, where 100 is 'the best health you can imagine' and 0 is 'the worst health you can imagine.' An increasing score indicates improvements from baseline. | Baseline and on Day 1 in Cycles 5, 9, 13, 17, 21, 25, 29, and 33 (21 days per cycle) and safety follow-up visit (up to 30 days after end of treatment; up to approximately 3 years and 1 week) | 
| Quality of Life Assessment: EORTC QLQ-C30 Change From Baseline in Global Health Status Score | Mean change from baseline at safety follow-up visit in EORTC QLQ-C30 Global Health Status/Quality of Life score. The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of cancer patients and includes global health status and quality of life questions related to their overall health in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Answers are converted to a score of 0 to 100, with a higher score indicating improved health status. | Baseline and on Day 1 in Cycles 5, 9, 13, 17, 21, 25, 29, and 33 (21 days per cycle) and safety follow-up visit (up to 30 days after end of treatment; up to approximately 3 years and 1 week) | 
| Quality of Life Assessment: EORTC QLQ-C30 Change From Baseline in Fatigue Score | Mean change from baseline at safety follow-up visit in EORTC QLQ-C30 Fatigue score. The EORTC QLQ-C30 v3.0 is a questionnaire that assesses quality of life of cancer patients and includes questions related to fatigue symptoms in which participants respond based on a 7-point scale, where 1 is very poor and 7 is excellent. Answers are converted to a score of 0 to 100, with a higher score indicating improved health status. | Baseline and on Day 1 in Cycles 5, 9, 13, 17, 21, 25, 29, and 33 (21 days per cycle) and safety follow-up visit (up to 30 days after end of treatment; up to approximately 3 years and 1 week) | 
| Number of Participants With Adverse Events | Number of participants with treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs), including clinically relevant changes in laboratory tests, physical examination, electrocardiogram, and vital signs | Up to approximately 3 years and 1 week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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T/NK-cell, NK/T-cell, extranodal, nasal, NK-cell, peripheral T-cell, anaplastic large cell, ALCL, angioimmunoblastic, PTCL-NOS, Relapsed, ENKTL, Refractory