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

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

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).

Study Overview

• Status: Completed
• Conditions: Cutaneous T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma, ALK-Positive; Extranodal NK/T-cell Lymphoma, Nasal Type; Peripheral T Cell Lymphoma; Extranodal NK/T-cell Lymphoma; Peripheral T-Cell Lymphoma, Not Otherwise Specified; Anaplastic Large Cell Lymphoma, ALK-negative; PTCL; Extranodal NK T Cell Lymphoma; Extranodal NK T Cell Lymphoma, Nasal; Angioimmunoblastic T-Cell Lymphoma Recurrent; Angioimmunoblastic T-Cell Lymphoma Refractory; Peripheral T-cell Lymphoma NOS; Peripheral T-Cell Lymphoma Refractory; ALK-negative Anaplastic Large Cell Lymphoma; ALK-Positive Anaplastic Large Cell Lymphoma
• Intervention / Treatment: Drug: Tislelizumab

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • UBC - British Columbia Cancer Agency - The Vancouver Centre
• China
  • Beijing
    • Beijing, Beijing, China, 100730
      • Peking Union Medical College Hospital
    • Beijing, Beijing, China, 100000
      • Peking University Third Hospital
    • Beijing, Beijing, China, 100730
      • Beijing Hospital
  • Fujian
    • Fuzhou, Fujian, China, 350001
      • Fujian Medical University Union Hospital
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center
  • He Nan
    • Zhengzhou, He Nan, China, 450008
      • He Nan Cancer Hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150000
      • Affiliated Tumor Hospital of Harbin Medical University
  • Jiangsu
    • Suzhou, Jiangsu, China, 215006
      • The First Affiliated Hospital of Soochow University
    • Xuzhou, Jiangsu, China, 221002
      • The Affiliated Hospital of Xuzhou Medical University
  • Shanghai
    • Shanghai, Shanghai, China, 200032
      • Fudan University Shanghai Cancer Center
    • Shanghai, Shanghai, China, 200092
      • Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital of Sichuan University
  • Tianjin
    • Tianjin, Tianjin, China, 300060
      • Tianjin cancer hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310022
      • Zhejiang Cancer Hospital
• France
  • Caen, France, 14000
    • Institut d'Hématologie de Basse Normandie
  • Limoges, France, 87000
    • Centre Hospitalier Universitaire de Limoges
  • Pierre-Bénite, France, 69310
    • Centre Hospitalier Lyon Sud
• Germany
  • Niedersachsen
    • Göttingen, Niedersachsen, Germany, 37075
      • Universitatsmedizin Gottingen
  • Sachsen
    • Leipzig, Sachsen, Germany, 04103
      • Universitätsklinikum Leipzig AöR
  • Sachsen-Anhalt
    • Halle, Sachsen-Anhalt, Germany, 06120
      • Universitätsklinikum Halle
• Italy
  • Emilia
    • Bologna, Emilia, Italy, 40138
      • Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola-Malpighi
    • Parma, Emilia, Italy, 43100
      • Ospedale Maggiore, AOU Parma
  • Liguria
    • Genova, Liguria, Italy, 16132
      • Ospedale Policlinico San Martino - IRCCS per l'Oncologia
  • Lombardia
    • Bergamo, Lombardia, Italy, 24127
      • ASST Papa Giovanni XXII
    • Milano, Lombardia, Italy, 20123
      • Ospedale San Raffaele
  • Toscana
    • Pisa, Toscana, Italy, 56126
      • A.O.U. Pisana, Stabilimento di Santa Chiara
  • Umbria
    • Terni, Umbria, Italy, 05100
      • Azienda Ospedaliera Santa Maria di Terni
• Taiwan
  • Tainan, Taiwan, 70403
    • National Cheng Kung University Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: ENKTL; 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; Administered intravenously; Other Names: BGB-A317
Experimental: Cohort 2: PTCL-NOS, AITL, and ALCL; 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; Administered intravenously; Other Names: BGB-A317
Experimental: Cohort 3: MF and SS; 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; Administered intravenously; Other Names: BGB-A317

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: BeiGene

Publications and helpful links

General Publications

• Huiqiang Huang, et al. Tislelizumab (BGB-A317) for relapsed/refractory extranodal NK/T-cell lymphoma: preliminary efficacy and safety results from a phase 2 study. Poster Abstract EP1268, European Hematology Association 2020.
• Pier Luigi Zinzani, et al. Tislelizumab (BGB-A317) for relapsed/refractory peripheral T-cell lymphomas: Safety and efficacy results from a phase 2 study. Poster Abstract EP1235, European Hematology Association 2020.

Study record dates

Study Major Dates

• Study Start (Actual): April 13, 2018
• Primary Completion (Actual): April 21, 2021
• Study Completion (Actual): April 21, 2021

Study Registration Dates

• First Submitted: April 4, 2018
• First Submitted That Met QC Criteria: April 9, 2018
• First Posted (Actual): April 10, 2018

Study Record Updates

• Last Update Posted (Actual): May 4, 2022
• Last Update Submitted That Met QC Criteria: April 29, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Relapsed; Refractory; nasal; PTCL-NOS; ALCL; extranodal; T/NK-cell; NK/T-cell; NK-cell; ENKTL; peripheral T-cell; anaplastic large cell; angioimmunoblastic
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphadenopathy; Neoplasms; Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, T-Cell; Lymphoma, T-Cell, Peripheral; Lymphoma, T-Cell, Cutaneous; Lymphoma, Large-Cell, Anaplastic; Lymphoma, Extranodal NK-T-Cell; Immunoblastic Lymphadenopathy
• Other Study ID Numbers: BGB-A317-207; 2017-003700-44 (EudraCT Number); CTR20171387 (Registry Identifier: Center for drug evaluation, CFDA)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No