DDR Genes Alteration and Response to Platinum-based Chemotherapy in Advanced Urothelial Cancer.

Exclusion Criteria

• •1. Previous treatment for metastatic or locally advanced disease.
• •2. Previous adjuvant therapy within 1 year from the diagnosis of metastatic disease.
• •3. Prior treatment with immunotherapy.
• •4. Previous or concurrent cancer that is distinct in primary site or histology from urothelial cancer within 3 years before enrollment EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors (Ta \[non-invasive tumor\], Tis \[carcinoma in situ\], and T1 \[tumor invades lamina propria\]), pT2 prostate cancer with PSA\<0.01.
• •5. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study medication
• •6. Pregnancy or breast-feeding. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of treatment, and a negative result must be documented before start of treatment.
• •7. Any cardiological condition among:
• •1. Congestive heart failure of New York Heart Association class 3 or worse.
• •2. Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months). Myocardial infarction less than 6 months before start of study drug.
• •3. Cardiac arrhythmias requiring anti-arrhythmic therapy (beta-blockers or digoxin are permitted).
• •4. Uncontrolled hypertension (systolic blood pressure \>150 mmHg or diastolic pressure \>90 mmHg despite optimal medical management).
• •5. Arterial or venous thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), pulmonary embolism within the 4 months before start of study medication.
• •8. Ongoing infection higher than National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 grade 2.
• •9. Known history of human immunodeficiency (HIV) virus infection or known history of chronic hepatitis B or C.
• •10. Any autoimmune disease that contraindicates the use of maintenance immunotherapy in case of stable or responsive disease to chemotherapy.
• •11. Seizure disorder requiring medication.
• •12. Symptomatic metastatic brain or meningeal tumors unless the patient is \>2 months from definitive therapy, has a negative imaging study within 4 weeks of study entry and is clinically stable with respect to the tumor at the time of study entry. Also, the patient must not be undergoing acute steroid therapy or tapering (chronic steroid therapy is acceptable provided that the dose is stable for 1 month before and after screening radiographic studies).
• •13. History of organ allograft.
• •14. Evidence or history of bleeding diathesis. Any hemorrhage or bleeding event of CTCAE grade 3 or higher within 4 weeks of start of study medication.
• •15. Non-healing wound, ulcer, or bone fracture.
• •16. Renal failure requiring hemodialysis or peritoneal dialysis.
• •17. Any illness or medical conditions that are unstable or could jeopardize the safety of the patient and his or her compliance in the study.
• •18. Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug. Administration of killed vaccines is allowed.
• •19. Participation to another clinical trial at the time of the enrollment.