Nivolumab in Combination With Ipilimumab in Patients With Metastatic Renal Cell Carcinoma

Prior treatment

• Uncontrolled CNS metastases. Patients with asymptomatic CNS metastases (at least 2 weeks after radiotherapy or surgery and steroids with prednisone equivalent of 10 mg or lower) are eligible
• More than one previous line of systemic therapy for mRCC
• Prior immunotherapy.
• Concurrent or recent (within 30 days of registration) treatment with any other experimental drug
• Concomitant use of other anti-cancer drugs or radiotherapy except for local pain control (radiotherapy of target lesion not allowed)
• Immunosuppressive medications (such as but not limited to: methotrexate, azathioprine, and TNF-α blockers) within 30 days before registration
  • Exception:
• systemic corticosteroids at doses not exceeding 10 mg/day of prednisone or equivalent
• inhaled and intranasal corticosteroids
• Live attenuated vaccination within 30 days prior to registration and for 30 days after last dose of any of the trial drugs. Inactivated viruses, such as those in the influenza vaccine, are permitted

Other illness

• History of hematologic or primary solid tumor malignancy, unless in remission for at least 3 years from registration with the exception of pT1-2 prostate cancer Gleason score \< 6, adequately treated cervical carcinoma in situ, or localized non-melanoma skin cancer.
• immunosuppressive medications for patients with contrast allergies
• History of or active auto-immune disease with the exception of diabetes mellitus type II
• Human immunodeficiency virus (HIV) infection or active chronic Hepatitis C or Hepatitis B Virus infection or any uncontrolled active systemic infection requiring intravenous (iv) antimicrobial treatment
• Known hypersensitivity to trial drug(s) or to any component of the trial drug(s)
• Any other serious underlying medical, psychiatric, psychological, familial or geographical condition, which in the judgment of the investigator may interfere with the planned staging, treatment and follow-up, affect patient compliance or place the patient at high risk from treatment-related complications.

• Written informed consent according to Swiss law and ICH/GCP regulations before registration and prior to any trial specific procedures
• Histologically or cytologically confirmed, locally advanced and/or metastatic clear cell RCC not amenable to surgery or definitive radiotherapy, and requiring systemic therapy
• Patient able and willing to provide serial biopsies and blood drawings (initial, at 14 weeks (except for patient in the expansion cohort), and at progression).
• Measurable disease
• In case of second line patients, the previous therapy must be stopped at least 2 weeks prior to registration
• Age ≥ 18 years
• WHO performance status of 0-1
• Bone marrow function: neutrophil count ≥ 1.5 x 109/L, platelet count ≥ 100 x 109/L
• Hepatic function: total bilirubin ≤ 1.5 x ULN (except for patients with Gilbert's disease ≤ 3.0 x ULN), AST, ALT and AP ≤ 2.5 x ULN (≤ 5 x ULN if significant hepatic metastasis is suspected to be the cause for enzyme elevation)
• Renal function: eGFR \> 20 mL/min/1.732
• Cardiac function: NYHA ≤ 2. In case of cardiac insufficiency NYHA 1 or 2, Left ventricular Ejection Fraction (LVEF) ≥ 35% as determined by echocardiography (ECHO) or multigated acquisition (MUGA) scan
• Women with child-bearing potential are using effective contraception are not pregnant or lactating and agree not to become pregnant during trial treatment and during 5 months thereafter. A negative pregnancy test before inclusion into the trial is required for all women with child-bearing potential.
• Men agree not to father a child during trial treatment and during 5 months thereafter