TREBL-2: Assessing the safety and immune system response to treatment with Tislelizumab, a type of immunotherapy, when given with other treatments, in people with Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV-DLBCL)An early phase, open label, multicentre, trial study to assess safety and efficacy of front-line therapy for EBV-associated Lymphomas 2

Exclusion

1. T cell lymphoma, transformed or 3B Follicular Lymphoma
2. CNS / meningeal / spinal cord involvement with lymphoma
3. Prior anti-PD-1 mAb
4. Active autoimmunity that might deteriorate when receiving an immunostimulatory agent. Note: Patients with the following diseases are not excluded and may proceed to further screening:
a. Controlled Type I diabetes
b. Hypothyroidism (provided it is managed with hormone replacement therapy only)
c. Controlled celiac disease
d. Skin diseases not requiring systemic treatment (eg, vitiligo, psoriasis, alopecia)
e. Any other disease that is not expected to recur in the absence of external triggering factors
5. Chronic prednisolone is greater than 10mg (or equivalent). Subjects requiring hormone replacement with corticosteroids are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses is equal to 10 mg or 10 mg equivalent prednisone per day. Administration of steroids through a route known to result in a minimal systemic exposure (topical, intranasal, intro-ocular, or inhalation) is acceptable.
6. Uncontrolled systemic infection, including active Hepatitis B/C. Patients with Hep B core Ab positive and Hep B surface antigen negative are permitted in the trial only if they have negative HBV DNA and must be on HBV prophylaxis (choice of prophylaxis is at physician’s discretion, with local guidance). Patients who are Hep B surface antigen positive are NOT allowed. Prior treated Hep C is allowed, provided HCV RNA is not detected.
7. As there is ‘chemo-free’ induction, patients requiring urgent cyto-reductive therapy for life-threatening disease are excluded. Requirement for urgent treatment due to life-threatening complications include for example: Compressive symptoms due to disease (which may or may not be bulky), such as superior vena caval obstruction; significant organ involvement causing compromise of organ function (including but not limited to liver, renal obstruction), malignant, symptomatic hypercalcaemia
8. Anticipated to be unable to receive full-dose R-CHOP
9. Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal, squamous cell skin cancer, low risk melanoma, superficial bladder cancer, localised cancer of the prostate cancer, cervix, or breast
10. Immunosuppression related lymphoma (e.g. PTLD, HIV, methotrexate).(Immunosuppression related lymphomas include those occurring after methotrexate, in patients with HIV, or following solid organ or haematopoietic stem cell transplant, and patients with inherited immunodeficiencies).
11. Previous treatment for current lymphoma (including chemotherapy, radiotherapy or investigational drug). Prior treatment for a histologically distinct lymphoma is permitted.
12. No concurrent uncontrolled medical condition as determined by investigator
13. Prior immune checkpoint blockade therapy
14. Use of pre-phase corticosteroids is discouraged (but permitted) due to the potential for reduction in Tislelizumab activity. However, if patients have received pre-phase steroids for symptom relief prior to screening they are not excluded.
15. Prior organ transplantation including allogeneic stem cell transplantation
16. Past history of interstitial lung disease (a rare side-effect of PD-1 blockade), non-infectious pneumonitis or uncontrolled diseases including pulmonary fibrosis, acute lung diseases, etc.)
17. Known severe hypersensitivity reactions to monoclonal antibodies (Grade 3 NCI-CTCAE v6), any history of anaphylaxis, or uncontrolled asthma (that is, 3 or more features of partially controlled asthma)
18. Major surgery for any reason, except diagnostic biopsy, within 4 weeks of enrolment and/or if the subject has not fully recovered from the surgery within 4 weeks of enrolment
19. Pregnancy or lactation.
20. Serious active co-morbid disease according to investigator’s discretion.
21. Previous adverse reaction to the trial drugs.
22. Any of the following cardiovascular risk factors:
a. Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, within 28 days (inclusive) before first dose of study drug
b. Pulmonary embolism within 28 days (inclusive) before first dose of study drug
c. Any history of acute myocardial infarction within 6 months (inclusive) before or first dose of study drug
d. Any history of heart failure meeting New York Heart Association (NYHA Classification III or IV within 6 months (inclusive) before or first dose of study drug
e. Any event of ventricular arrhythmia greater than or equal to Grade 2 in severity within 6 months (inclusive) before first dose of study drug
f. Any history of cerebrovascular accident within 6 months (inclusive) before first dose of study drug
g. Uncontrolled hypertension: systolic pressure greater than or equal to 160 mmHg or diastolic pressure greater than or equal to 100 mmHg despite anti-hypertension medications within 28 days (inclusive) before first dose of drug
h. Any episode of syncope or seizure within 28 days (inclusive) before first dose of study drug
23. Was administered a live vaccine within 4 weeks (inclusive) before first dose of study drug. COVID vaccines and seasonal vaccines for influenza are allowed.