A Study of BGB-A317 in Patients With Relapsed or Refractory Mature T- and NK- Neoplasms

Inclusion Criteria

To be eligible to participate in this study, a patient must meet all of the following
criteria:

1. Histologically confirmed diagnosis of relapsed or refractory, mature T-cell and
NK-cell neoplasms based on the WHO 2016 classification of tumors of hematopoietic and
lymphoid tissue. Patients will be allocated to one of two cohorts based on their
histologic diagnosis:

• Cohort 1: Extranodal NK/T-cell lymphoma (nasal or non-nasal type)

Patients with aggressive NK leukemia are excluded

• Cohort 2: Other mature T-cell neoplasms, limited to the following histologies:

Peripheral T-cell lymphoma - NOS

Angioimmunoblastic T-cell lymphoma

Anaplastic large cell lymphoma

2. Male or female ≥ 18 years of age at the time of informed consent (or acceptable age
according to local regulations, whichever is older)

3. Previously received 1 or more appropriate systemic therapies (eg, non-anthracycline
based regimens such as L asparaginase-based therapy) for cohort 1 and combination
chemotherapy (eg, CHOP, EPOCH, or similar therapy) for cohort 2. Radiation therapy
alone would not be acceptable previous therapy.

• For patients with relapsed or refractory anaplastic large cell lymphoma, regardless
of ALK status, must have received prior therapy with brentuximab vedotin (applicable
only to countries where brentuximab vedotin received marketing approval)

4. Disease progression during or after completion of most recent therapy or refractory
disease. Refractory disease is defined as failure to achieve CR or PR to most recent
therapy, and most recent therapy was an appropriate systemic therapy for mature T-cell
or NK-cell lymphoma

5. Measurable lesions defined as ≥ 1 lesion that is > 1.5 cm for nodal lesions and > 1 cm
for extranodal lesions

6. Availability of either unstained tissue (block or unstained slides) or stained slides,
and pathology report for central confirmation of mature T-cell or NK-cell lymphoma. If
stained slides or unstained tissue (block or unstained slides) are not available, a
fresh tumor tissue sample is mandatory for central pathology. Central pathology
confirmation is not required prior to enrollment.

7. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2

8. Has life expectancy ≥ 6 months

9. Patients 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. Adequate organ function defined as:

- Absolute neutrophil count (ANC) > 1000/mm3 (without growth factor support within
7 days of ANC measurement)

- Platelet > 50,000/mm3 (without growth factor support or transfusion within 7 days
of platelets measurement)

- Hemoglobin > 80 g/L (prior transfusion is acceptable)

- Creatinine clearance ≥ 30 ml/min (as estimated by the Cockcroft-Gault equation or
as measured by nuclear medicine scan or 24-hour urine collection)

- Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase, and
alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase ≤ 3.0 × upper
limit of normal (ULN)

- Serum total bilirubin < 2.0 × ULN (unless documented Gilbert's syndrome)

11. Female patients of childbearing potential must be willing to use a highly effective
method of birth control/contraception for the duration of the study, and for at least
120 days after the last dose of tislelizumab, and have a negative serum pregnancy test
within 7 days of the first dose of study drug.

12. Non-sterile males must be willing to use a highly effective method of birth
control/contraception for the duration of the study and for at least 120 days after
the last dose of tislelizumab

- Sterile males are those for whom azoospermia, in a semen sample examination, has
been demonstrated as definitive evidence of infertility

- Males with "low sperm counts" (consistent with "sub-fertility") are not to be
considered sterile for purposes of this study

13. Ability to provide written informed consent and can understand and comply with the
requirements of the study

Exclusion Criteria

To be eligible to participate in this study, a patient cannot meet any of the following
exclusion criteria:

1. Known central nervous system involvement by leukemia or lymphoma

2. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or anti CTLA 4
agent

3. Meets one of the following scenarios for hematopoietic stem cell transplantation
and/or chimeric antigen receptor T cell (CAR-T) therapy:

- Is eligible for autologous or allogeneic stem cell transplantation, unless
patient has refused transplantation

- Has undergone prior allogeneic hematopoietic stem cell transplantation or organ
transplantation

- Has received autologous stem cell transplantation within 6 months

- Has received CAR-T therapy within 12 months

4. Has received:

- Chemotherapy, targeted small molecule therapy, or radiation therapy within 2
weeks (or 5 half-lives, whichever is shorter) prior to study Day 1

- Recent treatment with another monoclonal antibody within 4 weeks prior to study
Day 1

- Investigational treatment or device within 4 weeks prior to study Day 1

- Or has not recovered from AEs (ie, ≤ Grade 1 or baseline level) due to prior
therapy. (Note: Patients with alopecia or ≤ Grade 2 neuropathy are an exception
to this criterion and may qualify for the study if all other criteria are met).

5. Concurrent or 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

6. Active autoimmune diseases or history of autoimmune diseases that may relapse

Note: Patients with the following diseases are not excluded and may proceed to further
screening:

- Type I diabetes under control

- Hypothyroidism (provided it is managed with hormone replacement therapy only)

- Controlled celiac disease

- Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis,
alopecia)

- Any other disease that is not expected to recur in the absence of external
triggering factors

7. Has known history of interstitial lung disease, non-infectious pneumonitis, pulmonary
fibrosis, acute lung diseases or evidence of dyspnea at rest or pulse oximetry of <
92% while breathing room air

8. Has any condition that required systemic treatment with either corticosteroids (> 10
mg daily of prednisone or equivalent) or other immunosuppressive medication within 14
days before study drug administration. Note: Patients who are currently or have
previously been on any of the following steroid regimens are not excluded:

- Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent)

- Topical, ocular, intra-articular, intranasal, or inhalational corticosteroid with
minimal systemic absorption

- Short course (≤ 7 days) of corticosteroid prescribed prophylactically (eg, for
contrast dye allergy) or for the treatment of a non-autoimmune condition (eg,
delayed-type hypersensitivity reaction caused by contact allergen

9. Has a known active TB (Bacillus Tuberculosis) infection

10. Known infection with HIV, human T-cell lymphotropic virus-1, -2, or serologic status
reflecting active hepatitis B or C infection as follows:

- Presence of hepatitis B surface antigen (HBsAg) or hepatitis B core antibody
(HBcAb). Patients with presence of HBcAb, but absence of HBsAg, are eligible only
if hepatitis B virus (HBV) DNA is undetectable by an assay with sensitivity ≤ 20
IU/mL. If so, patients may either undergo regularly scheduled monitoring of HBV
DNA or less frequent monitoring of HBV DNA while on prophylactic antiviral
medication as defined by regional standard of care. Patients may enter the study
on antiviral medication.

- Presence of hepatitis C virus (HCV) antibody. Patients with presence of HCV
antibody are eligible only if HCV RNA is undetectable.

11. Active fungal, bacterial, and/or viral infection requiring systemic therapy

12. Vaccination with a live vaccine within 35 days prior to the first dose of study drug

13. Clinically significant cardiovascular disease including the following:

- Myocardial infarction within 6 months before screening

- Unstable angina within 3 months before screening

- New York Heart Association Classification III or IV congestive heart failure

- History of clinically significant arrhythmias (eg, sustained ventricular
tachycardia, ventricular fibrillation, torsades de pointes)

- QTcF > 480 msecs based on Fredericia's formula

- History of Mobitz II second-degree or third-degree heart block without a
permanent pacemaker in place

- Uncontrolled hypertension as indicated by a minimum of 2 consecutive blood
pressure measurements showing systolic blood pressure > 170 mm Hg and diastolic
blood pressure > 105 mm Hg at screening

14. Major surgery within 4 weeks of the first dose of study drug

15. Ongoing alcohol or drug addiction

16. Underlying medical conditions that, in the opinion of the investigator and/or medical
monitor, will render the administration of study drug hazardous or obscure the
interpretation of safety or efficacy results

17. Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the pre-screening or screening visit
through 120 days after the last dose of trial treatment

18. Has hypersensitivity to tislelizumab or any of its excipients

19. History of severe hypersensitivity reactions to other monoclonal antibodies

20. Concurrent participation in another therapeutic clinical trial