A Study of Tislelizumab as Monotherapy in Relapsed or Refractory Classical Hodgkin Lymphoma

NCT ID: NCT03209973

Last Updated: 2025-02-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-04-21
• Study Completion Date: 2020-11-02

Brief Summary

The primary objective of this study was to evaluate the efficacy of tislelizumab assessed by Independent Review Committee (IRC) in participants with relapsed or refractory classical Hodgkin lymphoma (cHL), as measured by Overall Response Rate (ORR) per the Lugano Classification

Detailed Description

This was an open-label, single-arm, multi-center Phase 2 study. Response was to be assessed by PET(positron emission tomography) and computed tomography (CT) scan per the Lugano Classification. CT scan with contrast and Positron emission tomography (PET)/CT was used as required by protocol, until progressive disease (PD), new anti-cancer therapy, withdrawal of consent, death, lost to follow-up, or end of study (EOS), whichever occurred first. Total body magnetic resonance imaging (MRI) was allowed if CT with contrast is contraindicated. During treatment with immune checkpoint inhibitor such as with tislelizumab, pseudo-progression may occur due to immune cell infiltration and other mechanisms as manifested by apparent increase of existing tumor masses or appearance of new tumor lesions. Participants were allowed to continue study treatment if there is suspicion of pseudo-progression, provided they are asymptomatic and have radiographic progression only, until a second consecutive CT scan demonstrates PD at which time study treatment was discontinued permanently. Participants were evaluated for Adverse Events (AEs) (all Grades per National Cancer Institute Common Terminology Criteria for Adverse Events, Version 4.03 [NCI CTCAE v. 4.03]), serious AEs (SAEs), and any AEs requiring study drug interruption or discontinuation.

Conditions

Classical Hodgkin Lymphoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Tislelizumab

Tislelizumab 200 mg administered intravenously (IV) every-3-weeks (Q3W)

Group Type: EXPERIMENTAL

Tislelizumab

Intervention Type: DRUG

Administered as specified in the treatment arm

Interventions

Tislelizumab

Administered as specified in the treatment arm

Intervention Type: DRUG

Other Intervention Names

BGB-A317

Eligibility Criteria

Inclusion Criteria

1. Histologically confirmed relapsed or refractory cHL (biopsy from diagnosis or at any relapse is acceptable).

2. Participants must have relapsed (disease progression after most recent therapy) or refractory (failure to achieve complete Response (CR) /complete metabolic response [CMR] or partial response (PR) to most recent therapy) cHL and and failed to achieve a response or progressed after auto-SCT or meet the criteria of ineligible for auto-SCT.

3. Participants must have measurable disease defined as ≥ 1 nodal lesion that is > 1.5 cm in the longest diameter, or ≥ 1 extra-nodal lesion (e.g. hepatic nodules) that is > 1 cm in the longest diameter.

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

5. Life expectancy ≥ 12 weeks.

6. participants must have adequate organ functions as indicated by the following laboratory values:

1. Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, independent of growth factor support within 7 days of first dose.

2. Platelet ≥ 75 x 109/L, independent of growth factor support or transfusion within 7 days of first dose.

3. Hemoglobin (Hgb) ≥ 8 g/dL or ≥ 5 mmol/L.

4. Serum creatinine ≤ 1.5 x upper limit of normal (ULN).

5. Aspartate aminotransferase (AST)/glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/glutamic-pyruvic transaminase (SGPT) ≤ 2.5 x upper limit of normal (ULN), or ≤ 5X ULN if liver metastases are present.

6. Serum total bilirubin ≤ 1.5 x ULN (total bilirubin level < 4 x ULN for participants with Gilbert's syndrome).

7. International normalized ratio (INR) ≤ 1.5 x ULN and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy and coagulation parameters (prothrombin time [PT/INR] and aPTT) are within intended therapeutic range of intended use of the anticoagulant at time of Screening. Participants with factor inhibitors prolonging PT or INR may be included after discussion with the medical monitor.

8. Participants must have no evidence of dyspnea at rest and a pulse oximetry of > 92% while breathing room air.

9. Participants must have forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) > 60% by pulmonary function test (PFT); carbon monoxide diffusion capacity (DLCO), FEV1 and FVC all > 50 % predicted value; all PFTs must be obtained within 4 weeks prior to the first dose of tislelizumab.

Exclusion Criteria

1. Nodular lymphocyte-predominant Hodgkin lymphoma or gray zone lymphoma.

2. Prior allogeneic hematopoietic stem cell transplant.

3. History of severe hypersensitivity reaction to monoclonal antibodies.

4. New York Heart Association (NYHA) class III or IV heart failure, unstable angina, severe uncontrolled ventricular arrhythmia, electrocardiographic evidence of acute ischemia, or myocardial infarction within 6 months of first day of Screening.

5. Prior malignancy within the past 3 years except for curatively treated basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix or breast.

6. Prior therapy targeting PD-1 or PD-L1.

7. Participants with active autoimmune disease or history of autoimmune disease with high risk of recurrence including but not limited to history of immune-related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barrè syndrome, myasthenia gravis, systemic lupus erythematosus (SLE), connective tissue disease, scleroderma, inflammatory bowel disease including Crohn's disease and ulcerative colitis, autoimmune hepatitis, toxic epidermal necrolysis (TEN), or Stevens-Johnson syndrome.

Note: Participants is permitted to enroll if he/she has vitiligo, eczema, type I diabetes mellitus, endocrine deficiencies including thyroiditis managed with replacement hormone and/or physiologic corticosteroid. Participants with rheumatoid arthritis and/or other arthropathies, Sjögren's syndrome or psoriasis controlled with topical medication, and participants with positive serology such as positive antinuclear antibody (ANA) or anti-thyroid antibody should be evaluated for presence of target organ involvement and potential need for systemic treatment but should otherwise be eligible.

8. Conditions requiring systemic treatment with either corticosteroids (> 10 mg daily Prednisone equivalent) or other immunosuppressive medications within 14 days of first dose of tislelizumab.

Note: Adrenal replacement doses of ≤ 10 mg daily Prednisone are permitted in the absence of active autoimmune disease. Topical, ocular, intra-articular, intra-nasal and inhalational corticosteroid (with minimal systemic absorption), a brief course of corticosteroid for prophylaxis (e.g. contrast dye allergy) or for treatment of non-autoimmune conditions (e.g. delayed-type hypersensitivity reaction caused by contact allergen) are allowed.

9. Has history of interstitial lung disease or non-infectious pneumonitis or has evidence of interstitial lung disease or non infectious pneumonitis currently.

10. QT Interval Corrected by the Fridericia Correction Formula (QTcF)interval > 480 msec, unless secondary to bundle branch block.

11. Serious acute or chronic infection requiring systemic therapy.

12. Known central nervous system (CNS) lymphoma.

13. Underlying medical conditions that, in the Investigator's opinion, will render the administration of study drug hazardous or obscure the interpretation of toxicity or adverse events.

14. Autologous hematopoietic stem cell transplant within 100 days of first dose of tislelizumab.

15. Use of any live vaccine against infectious diseases (e.g. influenza, varicella, etc.) within 4 weeks (28 days) of the first dose of tislelizumab, and any intended use within 60 days after the last dose of tislelizumab.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

BeiGene

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: PRINCIPAL_INVESTIGATOR

BeiGene

Locations

Beijing Cancer Hospital

Beijing, Beijing Municipality, China

Chinese Pla General Hospital

Beijing, Beijing Municipality, China

Fujian Cancer Hospital

Fuzhou, Fujian, China

Henan Cancer Hospital

Zhengzhou, Henan, China

Tongji Hospital of Tongji Medical College Huazhong University of Science and Technology

Wuhan, Hubei, China

Jiangsu Province Hospital

Nanjing, Jiangsu, China

The First Hospital of Jilin University

Changchun, Jilin, China

Fudan University Shanghai Cancer Center

Shanghai, Shanghai Municipality, China

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Institute of Hematology and Hospital of Blood Disease

Tianjin, Tianjin Municipality, China

Tianjin Medical University Cancer Institute and Hospital

Tianjin, Tianjin Municipality, China

Zhejiang Cancer Hospital

Hangzhou, Zhejiang, China

Countries

China

References

Song Y, Gao Q, Zhang H, Fan L, Zhou J, Zou D, Li W, Yang H, Liu T, Wang Q, Lv F, Guo H, Yang L, Elstrom R, Huang J, Novotny W, Wei V, Zhu J. Treatment of relapsed or refractory classical Hodgkin lymphoma with the anti-PD-1, tislelizumab: results of a phase 2, single-arm, multicenter study. Leukemia. 2020 Feb;34(2):533-542. doi: 10.1038/s41375-019-0545-2. Epub 2019 Sep 13.

Reference Type: RESULT

PMID: 31520078 (View on PubMed)

Song Y, Gao Q, Zhang H, Fan L, Zhou J, Zou D, Li W, Yang H, Liu T, Wang Q, Lv F, Guo H, Zhao X, Wang D, Zhang P, Wang Y, Wang L, Liu T, Zhang Y, Shen Z, Huang J, Zhu J. Tislelizumab for Relapsed/Refractory Classical Hodgkin Lymphoma: 3-Year Follow-up and Correlative Biomarker Analysis. Clin Cancer Res. 2022 Mar 15;28(6):1147-1156. doi: 10.1158/1078-0432.CCR-21-2023.

Reference Type: DERIVED

PMID: 34716199 (View on PubMed)

Chen J, Zhang H, Zhu L, Zhao Y, Ding Y, Yuan Y. Tislelizumab for the treatment of classical Hodgkin's lymphoma. Drugs Today (Barc). 2020 Dec;56(12):781-785. doi: 10.1358/dot.2020.56.12.3233362.

Reference Type: DERIVED

PMID: 33332484 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CTR20170119

Identifier Type: REGISTRY

Identifier Source: secondary_id

BGB-A317-203

Identifier Type: -

Identifier Source: org_study_id