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

Anaplastic Large Cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03493451
• Other study ID #: BGB-A317-207
• Secondary ID: 2017-003700-44CT
• Status: Completed
• Phase: Phase 2
• Start date: April 13, 2018
• Est. completion date: April 21, 2021

Study information

• Verified date: April 2022
• Source: BeiGene
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: April 21, 2021
• Est. primary completion date: April 21, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Tislelizumab
Administered intravenously

Locations

Country	Name	City	State
Canada	UBC - British Columbia Cancer Agency - The Vancouver Centre	Vancouver	British Columbia
China	Beijing Hospital	Beijing	Beijing
China	Peking Union Medical College Hospital	Beijing	Beijing
China	Peking University Third Hospital	Beijing	Beijing
China	West China Hospital of Sichuan University	Chengdu	Sichuan
China	Fujian Medical University Union Hospital	Fuzhou	Fujian
China	Sun Yat-Sen University Cancer Center	Guangzhou	Guangdong
China	Zhejiang Cancer Hospital	Hangzhou	Zhejiang
China	Affiliated Tumor Hospital of Harbin Medical University	Harbin	Heilongjiang
China	Fudan university Shanghai Cancer Center	Shanghai	Shanghai
China	Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine	Shanghai	Shanghai
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	Tianjin Cancer Hospital	Tianjin	Tianjin
China	The affiliated hospital of Xuzhou medical university	Xuzhou	Jiangsu
China	He Nan Cancer Hospital	Zhengzhou	He Nan
France	Institut d'hématologie de Basse Normandie	Caen
France	Centre hospitalier Universitaire de Limoges	Limoges
France	Centre hospitalier Lyon Sud	Pierre-Bénite
Germany	Universitätsmedizin Göttingen	Göttingen	Niedersachsen
Germany	Universitätsklinikum Halle	Halle	Sachsen-Anhalt
Germany	Universitätsklinikum Leipzig AöR	Leipzig	Sachsen
Italy	ASST Papa Giovanni XXII	Bergamo	Lombardia
Italy	Azienda Ospedaliero-Universitaria di Bologna, Policlinico Sant'Orsola-Malpighi	Bologna	Emilia
Italy	Ospedale Policlinico San Martino - IRCCS per l'Oncologia	Genova	Liguria
Italy	Ospedale San Raffaele	Milano	Lombardia
Italy	Ospedale Maggiore, AOU Parma	Parma	Emilia
Italy	A.O.U. Pisana, Stabilimento di Santa Chiara	Pisa	Toscana
Italy	Azienda Ospedaliera Santa Maria di Terni	Terni	Umbria
Taiwan	National Cheng Kung University Hospital	Tainan
Taiwan	National Taiwan University Hospital	Taipei

Sponsors (1)

Lead Sponsor	Collaborator
BeiGene

Countries where clinical trial is conducted

Canada,  China,  France,  Germany,  Italy,  Taiwan, 

References & Publications (2)

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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