Atezolizumab and Bevacizumab Before Surgery for the Treatment of Resectable Liver Cancer

Exclusion Criteria

• •1. Patient has been treated for this malignancy, has another active malignancy, or has had an active malignancy within the last two years.
• •2. Patient has fibrolamellar HCC, sarcomatoid HCC, or mixed cholangiocarcinoma and HCC.
• •3. Patient has had a bleeding event due to untreated esophageal and/or gastric varices.
• •4. Patient has history of abdominal or tracheoesophageal fistula, GI perforation, or intra- abdominal abscess within 6 months of initiation of study treatment.
• •5. Patient has history of thrombosis, bleeding diathesis, History of Grade ≥ 4 venous thromboembolism, coagulopathy or significant vascular disease, serious, non-healing wound, active ulcer, or untreated bone fracture
• •6. Current or recent (\< 10 days prior to initiation of study treatment) use of aspirin (\> 325 mg/day), or clopidogrel (\> 75 mg/day) Note: The use of full-dose oral or parenteral anticoagulants for therapeutic purpose is permitted as long as the INR and/or aPTT is within therapeutic limits (according to institution standards) within 7 days prior to initiation of study treatment and the patient has been on a stable dose of anticoagulants for ≥ 2 weeks prior to initiation of study treatment. Prophylactic use of anticoagulants is allowed. However, the use of direct oral anticoagulant therapies such as dabigatran (Pradaxa) and rivaroxaban (Xarelto) is not recommended due to bleeding risk
• •7. Patient has history of hemoptysis within 30 days of initiation of study treatment.
• •8. Patient has serious cardiac disease, such as New York Heart association Grade II or greater congestive heart failure, MI, unstable angina, etc.
• •9. Patient has inadequately controlled hypertension (systolic ≥ 150 mmHg and/or diastolic ≥ 100 mmHg).
• •10. Patient has significant pulmonary disease (tuberculosis, pneumonia, pneumonitis, etc.).
• •11. Patient requires recurrent drainage procedures (pleural effusion, ascites, etc.).
• •12. Patient has had surgical procedure within 6 weeks of initiation of study treatment.
• •13. Patient has history of central nervous system disease.
• •14. Patient has history of severe allergic/anaphylactic reactions to chimeric or humanized antibodies or fusion proteins.
• •15. Patient has a knownhypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation.
• •16. Patient has known hypersensitivity to bevacizumab.
• •17. Patient has had any investigational agents within 28 days prior to initiation of study treatment.
• •18. Patient has history of severe infection within 4 weeks of initiation of treatment.
• •19. Patient has history of autoimmune disease or immune deficiency.
• •20. Patient has received a stem cell, liver, or other solid organ transplant.
• •21. Patient has history of other significant comorbidities that would be contraindicated for investigational treatment.
• •22. Patient has used:
• •* High dose steroids
• •* Vaccine of any kind within 4 weeks of initiating study treatment
• •* Oral or IV antibiotics within 2 weeks of initiating study treatment
• •* Immunostimulatory agents within 4 weeks of initiating study treatment
• •* Anticoagulation therapy (aspirin permitted)
• •* Total parenteral nutrition
• •23. Patient is pregnant or breastfeeding, or intention of becoming pregnant during study treatment or within5 months after the last dose of atezolizumab or 6 months after the last dose of atezolizumab
• •24. History of leptomeningeal disease
• •25. Uncontrolled tumor-related pain. Patients requiring pain medication must be on a stable regimen at study entry. • Symptomatic lesions (e.g., bone metastases or metastases causing nerve impingement) amenable to palliative radiotherapy should be treated prior to enrollment. Patients should be recovered from the effects of radiation. There is no required minimum recovery period. • Asymptomatic metastatic lesions that would likely cause functional deficits or intractable pain with further growth (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for loco-regional therapy if appropriate prior to enrollment
• •26. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). Patients with indwelling catheters (e.g., PleurX) are allowed.
• •27. Uncontrolled or symptomatic hypercalcemia (ionized calcium ≥ 1.5 mmol/L, calcium ≥12 mg/dL or corrected serum calcium ≥ULN)
• •28. Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab
• •29. Treatment with investigational therapy within 28 days prior to initiation of study treatment
• •30. Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
• •31. Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and interleukin 2 \[IL- 2\]) within 4 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
• •32. Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-TNF-α agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:
• •* Patients who received acute, low-dose systemic immunosuppressant medication or a one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible for the study.
• •* Patients who received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenal insufficiency are eligible for the study.