• Age ≥ 18 years on the day of signing informed consent.

• Metastatic or locally advanced (inoperable) type 2 or mixed PRCC, histologically confirmed by central review: FFPE blocks (or all HES and IHC slides) with the initial histology report must be sent for central reading before confirmation of inclusion in the study.

• No prior systemic treatment for renal cancer (chemotherapy, immunotherapy, anti-angiogenic drugs, or treatment under evaluation) even in adjuvant setting.

• At least one measurable site of disease according to RECIST v1.1.

• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) ≤ 1 evaluated within 7 days prior to the date of inclusion.

• In case of prior radiation therapy, discontinuation of irradiation for at least 3 weeks before first dose of study treatment, with at least 1 site kept/preserved for evaluation. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤ 2 weeks - limited field (\<10% of the whole body)) to non-CNS disease.

• Adequate bone-marrow, hepatic, and renal functions within 14 days prior to the inclusion, with:

‣ Hemoglobin ≥ 9.0 g/dl ou ≥ 5.6 mmol/l, neutrophils ≥ 1 000/mm3 (1.0 G/l), Platelets ≥ 100 000/mm3 (100 G/l),

⁃ Serum creatinine ≤ 2 x ULN OR creatinine clearance ≥ 50 ml/min/1.73m2 (calculated using either MDRD or CKD-EPI formula),

⁃ AST and ALT ≤ 2.5 x ULN (or ≤ 5 x ULN in case of liver metastasis),

⁃ Total serum bilirubin ≤ 1.5 x ULN (or direct bilirubin ≤ ULN for participants with total bilirubin levels \>1.5 × ULN),

• Absence of significant proteinuria (\<0.5 g/24h) confirmed by urinary dipstick test. If the dipstick test is ≥ 2+, proteinuria will be quantitated on a complete 24h urine sample (\< 1 g/l of protein/24h sample)

• Covered by a medical/health insurance.

⁃ Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures.

⁃ Patients of childbearing potential accepting to use effective contraception or abstain from heterosexual activity during study treatment and within 4 months after final dose of study therapy or being surgically sterile. Refer to Appendix 1 for approved methods of contraception.

⁃ Signed and dated approved informed consent form before any study specific procedures or assessments.