CLARA: Somatic and Germline Mechanisms That Impact Renal Cancer Immunotherapy

CLARA: Characterization of Somatic and Germline Mechanisms That Impact the Immunotherapy Treatment and Prognosis of Patients With Renal Cancer

The study is studying the joint contribution and interactions of germline variants and somatic mutations and their impact on Renal Cell Carcinoma (RCC) development and treatment (immunotherapy).

One hundred newly diagnosticated stage IV RCC patients will be recruited in the Ribeirao Preto Medical School.

Patients will be treated with immune checkpoint inhibitors (ICI) combination: nivolumab (3 mg/kg of body weight) plus ipilimumab (1 mg/kg) intravenously every three weeks for four doses, followed by nivolumab 480mg every four weeks, until progression, toxicity or complete two years of treatment.

Patients will be followed up for the clinical outcome (progression-free survival, best response, and overall survival).

Fresh-frozen primary tumor tissue will be collected for somatic genomic characterization.

Blood DNA will be genotyped for the identification of common germline variation, as well as ancestry determination.

Inclusion Criteria:

• Renal cell carcinoma patient: histological confirmed clear cell tumor;
• First-line metastatic treatment;
• Stage IV with at least one measured lesion;
• Fresh-frozen primary tumor tissue available;
• No previous immunotherapy or tyrosine kinase inhibitor treatment;
• All International Metastatic RCC Database Consortium (IMDC) Risk Score;
• Karnofsky Performance Scale (KPS) >=70;
• >=18 years old.

Exclusion Criteria:

• History of a known or suspected autoimmune disease;
• Any condition requiring systemic treatment with corticosteroids;
• Creatinine clearance < 40mL/min;
• Alanine aminotransferase (ALT) and/or Aspartate Aminotransferase (AST) > 5 x ULN;
• Pregnant women.