Individualized Treatment Strategy for Patients With Metastatic Non-clear Cell Renal Cell Carcinoma

Inclusion Criteria: 1. Signed informed consent form must be obtained before any study-related procedures start. 2. The patient must be willing and able to follow the protocol. 3. Age ≥ 18 years 4. Histological biopsy-confirmed inoperable, locally advanced or metastatic non-cc RCC or 100% sarcomatoid tumour arising from the kidney found unsuited for surgery with a curative intent. Nephrectomy is not mandatory. 1. If the primary disease was diagnosed more than 1 year ago, a fresh medium needle biopsy must be collected to confirm the diagnosis and tissue must be collected for DNA and RNA analyses. 2. If a patient with inoperable relapse had a nephrectomy less than 1 year ago, and no tissue samples are stored in Dansk CancerBiobank, a fresh medium needle biopsy must be collected for DNA and RNA analyses. 3. In cases where metastatic disease was confirmed by biopsy more than 1 year ago without initiated treatment, the patient is offered a fresh medium needle biopsy, but this is not mandatory for inclusion. 4. If the patient had a nephrectomy using tissue from Dansk CancerBiobank and has been diagnosed with metastases within 1 year, the patient must be offered a fresh medium needle biopsy from a metastasis if the metastasis is easily accessible for biopsy, but a fresh biopsy is not mandatory for inclusion. 5. A medium needle biopsy is mainly taken from a metastasis, but biopsy from a renal tumour is allowed. 6. A biopsy may not be taken from bones as it cannot be used for molecular analysis. 7. If the primary tumour is a proven clear cell RCC, but the biopsy from a metastasis shows non-cc RCC, the patient can be included in the study. 5. Sufficient tissue for DNA analyses, corresponding to 10 slides and RNA analyses corresponding to 1000 tumour cells. 6. Females with a negative pregnancy test or of non-childbearing potential (menopausal, hysterectomy or ovariectomy) and non-breastfeeding. 7. Females of childbearing potential (\<2 years after last menstrual period) and males must use effective contraception (pills, intrauterine device, diaphragm or condom with spermicide or sterilisation). 8. Measurable disease (according to RECIST 1.1 criteria) 9. Karnofsky Performance status ≥ 70% / ECOG Performance status 0-2. 10. Life expectancy more than 3 months. 11. At baseline, the laboratory values must be: Haematology: Leukocytes ≥ 3.0 x 109/l, thrombocytes ≥ 100 x 109/l, haemoglobin ≥ 6.2 mmol/l. 12. Biochemistry: International Normalized Ratio (INR) ≤ 1.5, APTT ≤ 1.5 x upper limit of normal (ULN) Total bilirubin ≤ 1.5 x ULN, aspartate transaminase, alanine aminotransferase ≤ 2.5 x ULN for patients without liver metastases, ≤ 5 x ULN for patients with liver metastases. Estimated glomerular filtration rate (eGFR) \> 30. Exclusion Criteria: 1. Previous systemic treatment for metastatic RCC (including neoadjuvant treatment). 2. Former adjuvant treatment with immune checkpoint inhibitors. 3. Major surgical procedure, open surgical biopsy or significant trauma within 28 days prior to initiation. 4. Serious non-healing wound, ulcer or bone fracture. 5. Auto-immune disease or other condition requiring systemic treatment with either corticosteroids (prednisolone \> 10 mg/day or similar) or other immunosuppressive drugs 6. Metastases in the central nervous system (CNS). The patient must have an MRI scan (preferred) or CT scan of the brain (using contrast agent if possible) within 28 prior to initiation. 7. Seizures which cannot be managed with standard medical treatment. 8. If urine dipstick with protein ≥ 3+, urine must be collected over a period of 24 hours which must be \< 3.5 grams/day. If degree 2 proteinuria, urine must be collected over a period of 24 hours prior to each prescription. 9. Other malignancy within 5 years (except for curatively treated basal cell carcinoma of the skin and/or cervix carcinoma in situ). 10. Uncontrolled hypertension (≥ 150 mm Hg systolic and/or ≥ 100 mm Hg diastolic) despite maximum antihypertensive medical treatment. 11. Clinically significant (i.e. active) cardiovascular disease, such as cerebrovascular conditions (≤ 6 months), myocardial infarction (≤ 6 months), unstable angina, New York Heart Association (NYHA) congestive heart failure ≥ degree III or serious cardiac arrhythmia requiring medical treatment. Patients with well-managed Atrial fibrillation/ atrial flutter may be included. 12. Treatment using other investigational drugs or participation in other studies. 13. Previous or current other diseases, metabolic dysfunction, clinical findings on physical examination or clinical laboratory findings that give suspicion of a disease or condition that would contraindicate the use of an investigational drug or a patient with a high risk of treatment complications. 14. Patients where the investigator finds that patient compliance prevents safe completion of the treatment.