Tislelizumab in People With Colorectal Cancer

Exclusion Criteria

• •* Histological confirmation of rectal adenocarcinoma
• •* Confirmation of dMMR by immunohistochemistry
• •* Rectal cancer stage II or III per AJCC 8 th edition criteria
• •* No evidence of distant metastases
• •* Hematological
• •Absolute neutrophil count (ANC) ≥1,500 /mm\^3
• •Platelets ≥100,000 / mcL
• •Hemoglobin \>9 g/dL or ≥5.6 mmol/L
• •* Renal
• •Serum creatinine OR measured or calculated creatinine clearance (GFR can also be used in place of creatinine or CrCl) ≤1.5 × upper limit of normal (ULN) OR ≥30 mL/min for subject with creatinine levels \> 1.5 × institutional ULN
• •* Hepatic
• •Serum total bilirubin ≤ 1.5 × ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels \> 1.5 ULN
• •AST (SGOT) and ALT (SGPT) ≤ 2.5 × ULN (\< 5 x ULN if hepatic metastases are present in cohort 1
• •* Coagulation
• •International Normalized Ratio (INR) or Prothrombin Time (PT) Activated Partial Thromboplastin Time (aPTT) INR \<1.5 or PT \<1.5 x ULN; and either PTT or aPTT \<1.5 x ULN. Patients on warfarin may be included on a stable dose with a therapeutic INR \<3.5
• •Presence of other active malignancy
• •Diagnosis of immunodeficiency or receiving systemic steroid therapy or other immunosuppressive therapy within 7 days prior to first dose of treatment
• •Any condition that required systemic treatment with either corticosteroids (\> 10 mg daily of prednisone or equivalent) or other immunosuppressive medication ≤ 14 days before first dose of study drug. Inhaled or topical steroids, and adrenal replacement doses \> 10 mg daily prednisone equivalents are permitted in the absence of an active autoimmune disease. Note: Patients who are currently or have previously been on any of the following steroid regimens are not excluded:
• •1. Adrenal replacement steroid (dose ≤ 10 mg daily of prednisone or equivalent)
• •2. Topical, ocular, intra-articular, intranasal, or inhaled corticosteroid with minimal systemic absorption
• •3. Short course (≤ 7 days) of corticosteroid prescribed prophylactically (eg, for contrast dye allergy) or for the treatment of a nonautoimmune condition (eg, delayed-type hypersensitivity reaction caused by contact allergen
• •Active autoimmune disease requiring systemic therapy within the 2 years prior to treatment initiation
• •o Well controlled hypothyroidism, diabetes, and skin conditions allowed
• •Untreated active Hepatitis B or Hepatitis C
• •o Patients actively on therapy with disease under control are allowed
• •Untreated Acquired Immunodeficiency Syndrome (AIDS)
• •o Patients with Human Immunodeficiency Virus (HIV) well controlled on anti-retroviral therapy are allowed
• •Infection (including tuberculosis infection, etc.) requiring systemic (oral or intravenous) antibacterial, antifungal, or antiviral therapy ≤ 14 days before first dose of study drug
• •History of interstitial lung disease, noninfectious pneumonitis, or uncontrolled lung diseases including pulmonary fibrosis.
• •o Patients with significantly impaired pulmonary function or who require supplemental oxygen at baseline must undergo an assessment of pulmonary function at screening
• •Currently receiving other anticancer or experimental therapy
• •Has received prior therapy with an immune checkpoint inhibitor
• •Prior ≥ Grade 3 immune-related AE from previous immunotherapy
• •Pregnant women, women who are breast-feeding, or men expecting to conceive or father children during the trial period, through 120 days after last dose of medication
• •Receipt of live vaccine within 30 days of planned treatment start
• •Major surgical procedure or significant traumatic injury within 28 days prior to enrollment
• •Known hypersensitivity to Tislelizumab
• •Prior allogeneic stem cell or organ transplantation
• •Any of the following cardiovascular risk factors:
• •a. Cardiac chest pain, defined as moderate pain that limits instrumental activities of daily living, ≤ 28 days before first dose of study drug b. Pulmonary embolism ≤ 28 days before first dose of study drug c. Any history of acute myocardial infarction ≤ 6 months before first dose of study drug d. Any history of heart failure meeting New York Heart Association Classification III or IV ≤ 6 months before first dose of study drug e. Any event of ventricular arrhythmia ≥ Grade 2 in severity ≤ 6 months before first dose of study drug f. Any history of cerebrovascular accident ≤ 6 months before first dose of study drug g. Uncontrolled hypertension that cannot be managed by standard antihypertension medications ≤ 28 days before first dose of study drug h. Any episode of syncope or seizure ≤ 28 days before first dose of study drug
• •Cohort 1 subjects
• •Prior immunotherapy, chemotherapy, radiation therapy, or surgery for metastatic colorectal cancer
• •o Treatment with adjuvant therapy of prior localized tumor is allowable as long as it was completed at least 6 months prior to cycle 1 day 1
• •Known active central nervous system (CNS) metastasis and/or carcinomatous meningitis
• •o Patients with previously treated brain metastases may participate if the brain metastases are stable via MRI assessment, performed ≥ 4 weeks after treatment
• •Cohort 2 subjects
• •Prior immunotherapy, chemotherapy, radiation therapy, or surgery for localized rectal cancer
• •Presence of metastatic or recurrent disease