Inclusion Criteria:
I1. Male or female patients aged ≥ 18 years at time of informed consent signature.
I2. Patient with histologically confirmed diagnosis of metastatic clear cell renal cell carcinoma (mccRCC) previously treated by at least 2 lines of therapy in the advanced/metastatic setting including at least 1 line of anti-VEGFR and 1 line of immunotherapy.
I3. Patient with documented radiological disease progression at the time of inclusion with measurable disease as per RECIST v1.1.
I4. Patient with PSMA-PET positive lesions (68Ga-PSMA-PET):
* For patient with only extrahepatic disease: ≥ 50% of positive extrahepatic metastatic lesions
* For patient with both extra-hepatic and liver metastasis: ≥ 50% of positive extrahepatic metastatic lesions and ≥ 80 % of positive supracentimetric liver metastatic lesions.
* For patient with only liver metastatic lesions: ≥ 80 % of positive supracentimetric lesions.
I5. Life expectancy ≥ 3 months.
I6. Eastern Cooperative Oncology Group performance status 0, 1 or 2.
I7. Demonstrate adequate organ function as defined in the protocol.
I8. Women of child-bearing potential must have a negative urine pregnancy test at screening (within 72 hours prior C1D1) and must agree to use 1 effective form of contraception from the time of the treatment period and of the negative pregnancy test up to 6 months after the last administration of study drug. Effective forms of contraception are listed in the protocol.
I9. Fertile males must use highly effective contraception during the dosing period and through 6 months after final administration of study drug.
I10. Patient should be able and willing to comply with study visits and procedures as per protocol.
I11. Patient should understand, sign, and date the written voluntary informed consent form at the screening visit prior to any protocol-specific procedures performed.
I12. Patients must be covered by medical insurance.
Exclusion Criteria:
E1. Patients with known active central nervous system (CNS) metastases and/or epidural metastases. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to C1D1 and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids (at doses higher than 10 mg/d of methylprednisolone or equivalent) for at least 4 weeks prior to C1D1.
E2. Patients previously treated with any radiopharmaceutical, excluding 68Ga-PSMA required during screening for this protocol.
E3. Persisting toxicities related to previous anti-cancer therapy which were not resolved to grade ≤1 (except: anaemia provided that criterion I7 is met) and /or any persistent irAE of any grade (except adequately controlled irAE (e.g: with replacement therapy for endocrine irAE)).
E4. History, within 2 years, of cancer other than renal cancer, except for basal or squamous cell carcinoma of the skin, in-situ carcinoma of the cervix, localized prostate cancer.
E5. History of idiopathic pulmonary fibrosis, non-infectious pneumonitis, interstitial lung disease that required steroids or has current pneumonitis, interstitial lung disease, drug-induced pneumonitis, or evidence of active pneumonitis on screening chest CT scan.
E6. Prior therapy or a need to be treated with a forbidden concomitant/concurrent therapies/procedure as defined per protocol.
E7. Patients with clinically significant hematuria, hematemesis, or hemoptysis exceeding 0.5 teaspoon (2.5 mL) of red blood, as well as those with a history of coagulopathy or other significant bleeding (e.g., pulmonary hemorrhage) within the 3 months prior to the initiation of the study treatment. Patients receiving anticoagulation medication will be eligible only if the dosage and route of administration have remained stable since at least 2 weeks prior to C1D1.
E8. Patients with an active uncontrolled infection. E9. Women pregnant or breastfeeding. E10. Patients placed under a legal protection regimen such as: Judicial Safeguards, curatorship or guardianship
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