A Study of Tislelizumab as Monotherapy in Relapsed or Refractory Classical Hodgkin Lymphoma
Condition: Classical Hodgkin Lymphoma
MeSH terms: Lymphoma; Hodgkin Disease
Intervention: Tislelizumab
Intervention description: Administered as specified in the treatment arm
Intervention MeSH terms: Tislelizumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 70.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

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
    

Eligibility 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.