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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03209973
Recruitment Status : Completed
First Posted : July 6, 2017
Results First Posted : October 12, 2020
Last Update Posted : November 18, 2021
Sponsor:
Information provided by (Responsible Party):
BeiGene

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

Condition or disease Intervention/treatment Phase
Classical Hodgkin Lymphoma Drug: Tislelizumab Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 70 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Single Arm, Multicenter, Phase 2 Study of BGB-A317 as Monotherapy in Relapsed or Refractory Classical Hodgkin Lymphoma
Actual Study Start Date : April 21, 2017
Actual Primary Completion Date : November 2, 2020
Actual Study Completion Date : November 2, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Tislelizumab
Tislelizumab 200 mg administered intravenously (IV) every-3-weeks (Q3W)
Drug: Tislelizumab
Administered as specified in the treatment arm
Other Name: BGB-A317




Primary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: From the date of first dose Up to approximately 3 year and 7 months ]
    ORR is defined as the proportion of participants who achieve a best response of Complete Response (CR) or Partial Response (PR), as assessed by Independent Review committee (IRC) per the Lugano Classification


Secondary Outcome Measures :
  1. Progression-free Survival (PFS) [ Time Frame: From the date of first dose until end of study (Up to approximately 3 years and 7 months) ]
    PFS is defined as the time from the first dose of tislelizumab to the date of Progressive Disease (PD) or death, whichever occurs first, assessed by IRC per the Lugano Classification

  2. Duration of Response (DOR) [ Time Frame: From the date of first dose until end of study (Up to approximately 3 years and 7 months) ]
    DOR is defined as the time from the date that response criteria are first met to the date that PD is objectively documented or death, whichever occurs first, assessed by IRC per the Lugano Classification

  3. Rate of Complete Response (CRR) [ Time Frame: From the date of first dose until end of study (Up to approximately 3 years and 7 months) ]
    CRR is defined as the percentage of participants who achieve a best response of CR, assessed by IRC per the Lugano Classification

  4. Time to Response (TTR) [ Time Frame: From the date of first dose until end of study (Up to approximately 3 years and 7 months) ]
    TTR is defined as the time from the date of the first dose of tislelizumab to the time the response criteria are first met, assessed by IRC per the Lugano Classification

  5. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [ Time Frame: From the date of first dose until end of study (Up to approximately 3 years and 7 months) ]

    An adverse event (AE) is defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study drug, whether considered related to study drug or not.

    An SAE is any untoward medical occurrence that, at any dose:

    • Results in death.
    • Is life-threatening.
    • Requires hospitalization or prolongation of existing hospitalization
    • Results in disability/incapacity
    • Is a congenital anomaly/birth defect
    • Is considered a significant medical AE by the investigator based on medical judgement

  6. Number of Participants With Significant Changes in Clinical Laboratory Results [ Time Frame: From the date of first dose until end of study (Up to approximately 3 years and 7 months) ]
    Clinical laboratory (e.g. hematology, serum chemistry, urinalysis) values were evaluated for each laboratory parameter and participants with clinically significant changes are summarized.

  7. Number of Participants With Significant Changes in Electrocardiograms [ Time Frame: From the date of first dose until end of study (Up to approximately 3 years and 7 months) ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key 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.
  10. Prior chemotherapy, radiotherapy, immunotherapy or investigational therapy (including Chinese herbal medicine and Chinese patent medicine) used to control cancer including locoregional treatment must have been completed ≥ 4 weeks before the first dose of tislelizumab, and all treatment-related adverse events are stable and have either returned to baseline or Grade 0/1 (except for alopecia and hemoglobin. For hemoglobin, please follow inclusion criteria #8c [hemoglobin]).

Key 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.

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03209973


Locations
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China, Beijing
Beijing Cancer Hospital
Beijing, Beijing, China, 100142
Chinese PLA General Hospital
Beijing, Beijing, China, 100853
China, Henan
Henan Cancer Hospital
Zhengzhou, Henan, China
China, Hubei
Tongji Hospital, Tongji Medical College Huazhong University of Science and Technology
Wuhan, Hubei, China
China, Jiangsu
Jiangsu Province Hospital
Nanjing, Jiangsu, China
China, Jilin
The First Affilliated Hospital of Jilin University
Changchun, Jilin, China
China, Shanghai
Fudan University Shanghai Cancer Center
Shanghai, Shanghai, China
China, Sichuan
West China Hospital of Sichuan University
Chengdu, Sichuan, China
China, Tianjin
Institute of Hematology and Blood disease hospital,Chinese Academy of Medical Science
Tianjin, Tianjin, China, 300020
Tianjin Medical Universtity Cancer Institute and Hospital
Tianjin, Tianjin, China, 300060
China, Zhejiang
Zhejiang Cancer Hospital
Hangzhou, Zhejiang, China
Sponsors and Collaborators
BeiGene
Investigators
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Principal Investigator: Study Director BeiGene
  Study Documents (Full-Text)

Documents provided by BeiGene:
Study Protocol  [PDF] July 15, 2019
Statistical Analysis Plan  [PDF] July 17, 2018

Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: BeiGene
ClinicalTrials.gov Identifier: NCT03209973    
Other Study ID Numbers: BGB-A317-203
CTR20170119 ( Registry Identifier: Center for drug evaluation, CFDA )
First Posted: July 6, 2017    Key Record Dates
Results First Posted: October 12, 2020
Last Update Posted: November 18, 2021
Last Verified: October 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Hodgkin Disease
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases