hARnessing CAbozantinib and Durvalumab Immuno-oncology Association: ARCADIA Study"

Inclusion Criteria: * Written informed consent. * Age ≥18 years. * Body weight \>30kg * Histologically-confirmed diagnosis of UC or variant histologies (e.g. squamous cell carcinoma, adenocarcinoma, micropapillary tumors, BUT excluding pure small cell carcinoma) of the bladder or the urothelium. * Either bladder, urethral, or upper tract primary tumor will be allowed. * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. * Life expectancy of at ≥ 12 weeks. * Availability of tumor tissue for PD-L1 IHC assay. * Measurable and non-measurable disease will be included (e.g. patients with bone metastases only will be allowed for inclusion). * Failure of 1 or 2 cisplatin-based conventional chemotherapy regimens for metastatic disease (2nd-to-3rd line only). * Neoadjuvant/adjuvant regimens will be counted provided that a relapse occurred with 6 months of the last cycle of chemotherapy. * Adequate function of the organs: 1. Absolute neutrophil count (ANC) ≥ 1500/mm3 2. Platelets ≥ 100,000/mm3 3. Hemoglobin ≥ 9 g/dL (≥ 90 g/L). 4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 3.0 × upper limit of normal. 5. Total bilirubin ≤ 1.5 × the upper limit of normal. For subjects with Gilbert's disease ≤ 3 mg/dL g. Serum creatinine ≤ 2.0 × upper limit of normal or calculated creatinine clearance ≥ 30 mL/min using the Cockroft-Gault equation h. Lipase \< 2.0 times the upper limit of normal (ULN) * Recovery to baseline or ≤ Grade 1 Common Terminology Criteria for Adverse Events (CTCAE) v5.0 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy * Ability to swallow tablets * Contraception for sexually active fertile patients and their partners. Of note, a barrier method is recommended in addition to the use of steroid hormonal contraceptives, because the effects of cabozantinib on the pharmacokinetics of the latter are unknown. * Evidence of post menopausal status or serum pregnancy test for female pre-menopausal subject Exclusion Criteria: * Patients taking regular oral steroids, above the allowed limit of 10mg/day methylprednisolone or analogues, for any reason. Patients must not have had steroids for 28 days prior to study entry. * Malignancies other than bladder carcinoma within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) or localized prostate cancer treated with curative intent and absence of prostate-specific antigen (PSA) relapse or incidental prostate cancer (Gleason score ≤ 3 + 4 and PSA \< 10 ng/mL undergoing active surveillance and treatment naive). * Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results. * Active or untreated CNS metastases as determined by computed tomography (CT) or magnetic resonance imaging evaluation during screening and prior radiographic assessments. * Patients with treated asymptomatic CNS metastases are eligible, provided they meet all of the following criteria: 1. Evaluable or measurable disease outside the CNS 2. No metastases to midbrain, pons, medulla, or within 10 mm of the optic apparatus (optic nerves and chiasm) 3. No history of intracranial or spinal cord hemorrhage 4. No ongoing requirement for corticosteroid as therapy for CNS disease; anti-convulsants at a stable dose are allowed 5. No evidence of significant vasogenic edema 6. No stereotactic radiation, whole-brain radiation or neurosurgical resection within 4 weeks prior to Cycle 1, Day 1 7. Radiographic demonstration of interim stability (i.e., no progression) between the completion of CNS-directed therapy and the screening radiographic study 8. Screening CNS radiographic study ≥ 4 weeks since completion of radiotherapy or surgical resection and ≥ 2 weeks since discontinuation of corticosteroids * Pregnant female patients. All female patients of childbearing potential with a positive pregnancy test within 2 weeks prior to the first dose of study treatment will be excluded from the study. * Clinically significant cardiovascular disease, for example, myocardial infarction (within 3months prior to enrolment), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure or serious cardiac arrhythmia requiring medication (beta-blockers and digoxin are allowed) * Uncontrolled hypertension, stroke or other ischemic or thromboembolic event (DVT, PE) within 6 months before first dose of cabozantinib. * Severe infections within 4 weeks prior to enrolment in the study including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia. * Major surgical procedure within 4 weeks prior to enrolmentor anticipation of need for a major surgical procedure during the course of the study other than for diagnosis. Complete wound healing from major surgery must have occurred 1 month before inclusion and from minor surgery (eg, simple excision, tooth extraction) at least 10 days before inclusion. Subjects with clinically relevant ongoing complications from prior surgery are not eligible. * Received therapeutic oral or intravenous (IV) antibiotics within 2 weeks prior to enrolment (patients receiving prophylactic antibiotics, e.g., for prevention of a urinary tract infection or chronic obstructive pulmonary disease, are eligible). * Concomitant anticoagulation with oral anticoagulants or platelet inhibitors. * History of autoimmune disease including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. * Patients with a history of autoimmune-related hypothyroidism, unless on a stable dose of thyroid-replacement hormone. * Patients with uncontrolled Type 1 diabetes mellitus * Uncontrolled hypercalcemia (\> 1.5 mmol/L ionized calcium or Ca \> 12 mg/dL or corrected serum calcium \> ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab. Patients who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who do not have a history of clinically significant hypercalcemia are eligible. Patients who are receiving denosumab prior to enrollment must be willing and eligible to receive a bisphosphonate instead while on study. * radiation therapy for bone within 2 weeks or other radiation therapy within 4 weeks before first dose of study treatment. patients with clinically relevant ongoing complications from prior radiation therapy * serious non healing wound/ulcer/bone fracture, moderate to severe hepatic impairment (Child Pugh B or C) * History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan (History of radiation pneumonitis in the radiation field (fibrosis) is permitted). * Patients with tumors invading major pulmonary vessels and/or with cavitating pulmonary lesions. * Positive test for HIV. * Patients with active hepatitis infection (defined as having a positive hepatitis B surface antigen \[HBsAg\] test at screening) or hepatitis C. Patients with past hepatitis B virus (HBV) infection or resolved HBV infection (defined as having a negative HBs Ag test and a positive antibody to hepatitis B core antigen \[anti-HBc\] antibody test) are eligible. Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA. * Patients with active tuberculosis. * Gastrointestinal disorders likely to interfere with absorption of the study drug (e.g. partial bowel obstruction or malabsorption). * Subjects with gastrointestinal disorders associated with a high risk of perforation or fistula formation * Subjects with active peptic ulcer or with a history of clinically significant GI bleeding within 12 weeks before the first dose of study treatment * Prior treatment with CD137 agonists, anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents. * Administration of a live, attenuated vaccine within 4 weeks prior to enrolment or anticipation that such a live, attenuated vaccine will be required during the study. * Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to enrolment. * Treatment with systemic immunostimulatory agents (including but not limited to interferons or interleukin \[IL\]-2) within 4 weeks or five half-lives of the drug, whichever is shorter, prior to enrolment. * Rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption