Patient description: The patient is a 55-year-old man diagnosed with HCV 2 years ago and the recent coinfection with HBV. His past medical history is non-significant. He is on IFN, RBV and direct antiviral drugs for the past 6 months. The patient takes no other medications. His medical records show previous positive HCV RNA tests and a positive enzyme immunoassay for anti-HCV-antibodies. The recent biopsy was negative for hepatocellular carcinoma and was only remarkable for chronic inflammation compatible with a chronic viral hepatitis. There is no evidence of alcoholic liver disease, bleeding from esophageal varices, hemochromatosis, autoimmune hepatitis, or metabolic liver disease. He is an alert male with no acute distress. His BP: 130/75, HR: 90/min and BMI: 27. His abdomen is soft with no ascites or tenderness. The lower extremities are normal with no edema.

Clinical trial eligibility criteria: eligible ages (years): 18.0-999.0,  Breast Cancer HER2-positive Breast Cancer Female or male, age >= 18 years. 2. Local histologically confirmed HER2-positive unresectable, loco-regional or metastatic breast cancer. HER2-positive according to ASCO CAP 2018 guidelines defined as: 1. ISH testing with ERBB2-amplification as demonstrated by ratio ERBB2/centromeres >= 2.0 or mean gene copy number >= 6 OR 2. 3+ staining by immunohistochemistry (IHC). 3. Have sufficient tumour material available for assessment of PD-L1 and TIL status, as well as for correlative research 4. Confirmed PD-L1 positive or PD-L1 negative status evaluated by immunohistochemistry (IHC) to determine treatment cohort 5. Must have previously received trastuzumab, pertuzumab and T-DM1 in either the (neo) adjuvant or advanced disease setting. Any number of prior lines of anti-HER2 therapy is acceptable. 6. Have progression of unresectable locally advanced or metastatic breast cancer after last systemic therapy (as confirmed by investigator), or be intolerant of last systemic therapy. 7. Have measurable disease assessable by v1.1. 8. Have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 9. Have a life expectancy of at least 6 months, in the opinion of the investigator. 10. Have adequate haematological, coagulation, hepatic and renal functions within 7 days before registration as defined as: 1. Absolute neutrophil count (ANC) >= 1.5 x 10^9/L 2. Platelet count >= 100 x 10^9/L 3. Haemoglobin >= 90 g/L 4. Creatinine <= 1.5 x ULN or serum creatinine clearance > 40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance. Females: 5. Serum total bilirubin <= 1.5 x institutional upper limit of normal (ULN). In the case of known Gilbert's disease, serum total bilirubin < 2 x ULN is allowed 6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) <= 2.5 x institutional ULN unless liver metastases are present, in which case it must be <= 5 x ULN 7. International normalised ratio (INR) and activated partial thromboplastin time (aPTT) <= 1.5 x ULN unless on medication known to alter INR and aPTT (Note: Warfarin and other coumarin derivatives are prohibited). 11. Have a left ventricular ejection fraction (LVEF) of >= 50% as assessed by echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) documented within 4 weeks before registration. 12. Evidence of post-menopausal status or negative urine or serum pregnancy test for female pre-menopausal participants. Women will be considered post-menopausal if they have been amenorrhoeic for 12 months without an alternative medical cause. The following age-specific requirements apply: 1. Women < 50 years of age would be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of exogenous hormonal treatments or chemotherapy (whichever is most recent) and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy). 2. Women >= 50 years of age would be considered post-menopausal if they have been amenorrhoeic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses > 1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilisation (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). 13. Women of childbearing potential (WOCBP) and men with partners of childbearing potential must agree to use a highly effective barrier contraception from the signing of informed consent until 7 months after the last dose of protocol treatment 14. Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations during both the treatment and follow-up phases. 15. Must have one of the following (based on screening brain MRI): 1. No evidence of brain metastases OR 2. Untreated brain metastases not needing immediate local therapy. Participants with CNS measurable disease by 1.1, without measurable extracranial disease by are eligible. For participants with untreated CNS lesions > 2.0 cm on screening MRI, discussion with and approval from BCT and the Study Chair is required before registration OR 3. Previously treated brain metastases: i) Brain metastases previously treated with local therapy may either be stable since treatment or may have progressed since prior local CNS therapy, provided that there is no clinical indication for immediate re-treatment with local therapy in the opinion of the investigator. ii) Participants treated with CNS local therapy for newly identified lesions found on initial MRI performed during screening for this study may be eligible if the following are met: 1. Time since whole brain radiation therapy (WBRT) is >= 21 days before registration, or 2. Time since surgical resection is >= 7 days before registration, or time since surgical resection is >= 28 days 3. Other sites of disease assessable by 1.1. are present. iii) Relevant records of any CNS treatment must be available to allow for classification of target and non-target lesions  Previously treated with: 1. Lapatinib within 12 months of registration OR 2. Neratinib, afatinib, or other investigational HER2/epidermal growth factor receptor (EGFR) or HER2 tyrosine kinase inhibitor (TKI) within 12 months of registration, unless ceased due to toxicity and not progression. 2. Prior therapy with anti-PD-1, anti PD-L1/, L2 or anti-CTLA4 therapy. 3. Previous severe hypersensitivity reaction to treatment with a biologically similar TKI or monoclonal antibody. 4. Have received treatment with any systemic anti-cancer therapy (including hormonal therapy), non-CNS radiation or experimental agent within 28 days of registration. a) GnRH therapy can continue in pre-menopausal women with ER-positive breast cancer who were receiving it before study entry. 5. Have any toxicity related to prior cancer therapies that has not resolved to <= Grade 1, with the following exceptions: 1. Alopecia 2. Neuropathy, which must have resolved to <= Grade 2 3. Menopausal symptoms. 6. Any untreated brain lesions > 2.0 cm in size, unless discussed with BCT and Study Chair and approval for registration is given. 7. Ongoing use of systemic corticosteroids for control of symptoms of brain metastases at a total daily dose of > 2 mg of dexamethasone (or equivalent). However, patients on a chronic stable dose of <= 2 mg total daily of dexamethasone (or equivalent) may be eligible with discussion and approval by BCT and the Study Chair. 8. Any brain lesion thought to require immediate local therapy, including (but not limited to) a lesion in an anatomic site where increase in size or possible treatment-related oedema may pose risk to patient (e.g. brain stem lesions). Participants who undergo local treatment for such lesions identified by screening contrast brain MRI may still be eligible for the study based on described under 15. 9. Known or suspected leptomeningeal disease as documented by the investigator. 10. Have poorly controlled (> 1/week) generalised or complex partial seizures, or manifest neurologic progression due to brain metastases notwithstanding CNS-directed therapy. 11. History of clinically significant or uncontrolled cardiac disease, including congestive heart failure (New York Heart Association functional classification ≥ 3), angina, myocardial infarction or ventricular arrhythmia. Have known myocardial infarction or unstable angina within 6 months before registration. 12. Active infection requiring systemic therapy. 13. Active or history of autoimmune disease or immune deficiency, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions: 1. History of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible 2. Stable diabetes mellitus are eligible 3. Eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g. patients with psoriatic arthritis are excluded) are eligible provided ALL the following conditions are met: i) Rash must cover < 10% of body surface area ii) Disease is well controlled at baseline and requires only low-potency topical corticosteroids iii) No occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors, or high-potency or oral corticosteroids within the previous 12 months. 14. Chronic systemic therapy with either corticosteroids (> 10 mg daily prednisone or equivalent) or other immunosuppressive medications within 7 days before registration. Inhaled or topical steroids, and adrenal replacement steroid > 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. Replacement therapy (e.g. thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Participants requiring steroids as a once-off, short term anti-emetics (such as that prescribed with chemotherapy) are allowed. 15. Administration of a live vaccine within 30 days before registration. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed, however intranasal influenza vaccines (e.g. FluMist(R)) are live attenuated vaccines and are not allowed. 16. Known human immunodeficiency virus (HIV) (HIV1/2antibodies) or active Hepatitis B (HBsAg reactive) or Hepatitis C (HCV RNA [qualitative]). 1. Participants with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen antibody test) are eligible 2. Participants positive for HCV antibody are eligible only if polymerase change reaction is negative for HCV RNA. 17. Pregnant, breastfeeding or planning a pregnancy; lactating participants must stop breast feeding before registration. Use of oral, injectable or implant hormonal contraceptives or medicated IUD must stop before registration. 18. Require therapy with warfarin or other coumarin derivatives (non-coumarin anticoagulants are allowed). 19. Unable to swallow pills or has significant gastrointestinal disease which would preclude the adequate oral absorption of medications. 20. Use of a strong CYP2C8 inhibitor within 5 half-lives of the inhibitor, or a strong CYP3A4 or CYP2C8 inducer within 5 days before registration. Use of sensitive CYP3A substrates should be avoided 2 weeks before registration and during study treatment. 21. Treatment with botanical preparations (e.g. herbal supplements) and traditional Chinese medicines, intended for general health support or to treat the disease under study, within 7 days before registration. 22. Interstitial lung disease. 23. History of or active pneumonitis requiring treatment with steroids. 24. History of active tuberculosis. 25. Has had an allogenic tissue/solid organ transplant. 26. Known history of uncontrolled hypertension (>= 180/110), unstable diabetes mellitus, dyspnoea at rest, or chronic therapy with oxygen. 27. Considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, or any psychiatric disorder or psychosocial situation that prohibits obtaining informed consent