PRadR 2 - A single center, open-label, Phase I study evaluating 161Tb-PSMA therapy in adult patients with metastatic clear cell renal cell carcinoma

Prior treatment

• E1. Patients with known active central nervous system (CNS) metastases and/or epidural metastases and/or leptomeningitis. 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.
• E3. Persisting AEs related to previous anti-cancer therapy which were not resolved to grade ≤ 1 (except: anemia provided that criterion I7 is met) and /or any persistent immune-related AEs >1 (except adequately controlled irAE, e.g.: with replacement therapy for endocrine irAE).
• E6. Prior therapy or needs to be treated with a forbidden concomitant/concurrent therapies/procedures including: see table in exclusion criteria
• E7. Patients with clinically significant hematuria, hematemesis or hemoptysis exceeding 0.5 teaspoon (2.5mL) 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 for at least 2 weeks prior to C1D1.

Other illness

• E4. History, within 2 years, of cancer other than renal cancer, except for basal or squamous cellcarcinoma of the skin, in situ carcinoma of the cervix or 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.
• E8. Patients with an active uncontrolled infection.

Other

• E9. Pregnant or breastfeeding women.

• I1. Male or female patients aged ≥ 18 years at time of informed consent signature.
• I9. Fertile males must use a highly effective contraception during dosing period and through 6 months after final administration of study.
• 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. Covered by a medical insurance.
• I10. Patient should be able and willing to comply with study visits and procedures as per protocol.
• I2. Patient with histologically confirmed diagnosis of metastatic clear cell renal cell carcinoma (mccRCC) progressing during or after at least 2 lines of therapy 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 positive PSMA-PET (68Ga-PSMA-PET) (see Appendix 6): o For patient with only extrahepatic disease: ≥ 50% of positive extrahepatic lesions o For patient with both extra-hepatic and liver metastasis: ≥ 50% of positive extrahepatic metastatic lesions and ≥ 80 % of positive supracentimetric liver metastatic lesions. o For patient with only liver metastatic lesions: ≥ 80 % of positive supracentimetric lesions
• I5. Life expectancy ≥ 6 months.
• I6. Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1, with a Karnofsky Performance Status (KPS) ≥ 80%.
• I7. Adequate organ function according to laboratory values defined below : See table in inclusion criteria
• I8. Women of child-bearing potential must have a negative pregnancy test at screening (within 72 hours prior C1D1) and must agree to use 1 highly 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 IMP. Effective forms of contraception are listed in Appendix 5.