CD70-Targeted Immuno-PET/CT-Directed Free of Therapy Used for mccRCC Patients With IMDC Favorable or Intermediate Risk

Prior treatment

• Prior systemic therapy for advanced RCC
• Active brain metastases or leptomeningeal disease unless adequately treated with radiotherapy and/or surgery (including radiosurgery) who are clinically stable without progression prior to treatment

Other illness

• Concurrent or prior invasive malignancies within the past 5 years, except adequately treated in situ/superficial cancers (e.g., non-melanoma skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix/breast)
• Presence of uncontrolled major comorbidities or recent severe illnesses within 6 months, including but not limited to: uncontrolled hypertension, clinically significant cardiovascular disease, GI disorders with high risk of perforation/fistula, significant hematuria, hematemesis, hemoptysis, major bleeding history, severe active infections (including active HIV, HBV, or HCV), or severe autoimmune diseases (e.g., systemic lupus erythematosus, immune pneumonitis)
• Known allergy or hypersensitivity to the CD70 imaging agent or any of its excipients
• Severe hepatic or renal insufficiency, or inability to tolerate PET/CT examination
• Medical/psychiatric/social conditions compromising protocol compliance
• Failure to complete 12 months(±1m) of first-line PD-1/PD-L1 + VEGFR-TKI therapy due to unmanageable toxicity or disease progression
• Failure or inability to undergo CD70-targeted immuno-PET/CT scan at the 12-month evaluation timepoint

Other

• STEP0: At Treatment Initiation
• Poor risk as per International Metastatic RCC Database Consortium (IMDC) criteria
• Karnofsky Performance Status (KPS) \<70%
• Inadequate organ and bone marrow function
• Life expectancy \< 6 months
• Pregnancy, lactation, or refusal of contraception during and for 5 months post-treatment
  • STEP1: At 12-Month Evaluation
• Unacceptable clinical deterioration or investigator discretion indicating that a treatment holiday is not in the best interest of the patient

• STEP0: At Treatment Initiation
• Male or female subjects aged ≥ 18 years
• Locally advanced (not amenable to curative surgery or radiation therapy) or metastatic RCC (American Joint Committee on Cancer \[AJCC\] Stage IV)
• Histologically or cytologically confirmed advanced RCC with predominantly clear-cell subtype
• Favorable or intermediate risk as per International Metastatic RCC Database Consortium (IMDC) criteria
• Karnofsky Performance Status (KPS) grade ≥ 70%
• At least one measurable lesion on CT per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• At least one high-uptake target lesion on CD70-targeted immuno-PET/CT per Positron Emission Tomography Response Criteria in Solid Tumors (PERCIST) version 1.0
• If CD70-negative lesions (visible on CT but lacking CD70 avidity on PET/CT) are present at baseline, they must meet ALL the following conditions: cannot be target lesions, cannot be located in major involved organs, must be ≤ 3 in number, and must account for ≤ 30% of the total tumor burden
• Adequate organ and bone marrow function meeting all laboratory criteria:
  • Absolute neutrophil count (ANC) ≥ 1.5 × 10\^9/L; Platelet count ≥ 100 × 10\^9/L; Hemoglobin ≥90 g/L
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \< 2.5 × upper limit of normal(ULN) (or ≤ 5 × ULN if hepatic metastases are present). Total bilirubin ≤ 1.5 × ULN (≤ 3 mg/dL if Gilbert's syndrome)
  • Serum creatinine ≤ 2.0 × ULN or estimated glomerular filtration rate (eGFR) ≥ 30 mL/min using the Cockcroft-Gault formula
• Capacity to comprehend and comply with protocol requirements, with documented informed consent signed
• Contraception agreement for sexually active fertile participants and partners to use medically accepted methods during the study and continue for 5 months after last treatment
• Negative pregnancy status at screening for women of childbearing potential
  • STEP1: At 12-Month Evaluation
• Patient met all eligibility criteria outlined above
• Patient must receive 12 months (±1m) of first line PD-1/PD-L1 ICI + VEGFR-TKI therapy, without permanent discontinuation of both agents due to unmanageable toxicity
• Patient must have completed an CD70-targeted immuno-PET/CT scan at 12m (±1m) from start of initial therapy
• Patients must meet one of the following criteria:
  • Eligible for treatment discontinuation: For CD70-Positive Lesions: Sustained Disease Control (Complete Response \[CR\], Partial Response \[PR\], or Stable Disease \[SD\]) on CT for ≥ 12 weeks per RECIST 1.1, AND achieved Complete Metabolic Response (CMR) or Partial Metabolic Response (PMR) on CD70 immuno-PET/CT per PERCIST 1.0 criteria; For CD70-Negative Lesions (If present at baseline): Must achieve a deep anatomical response, defined as Complete Response (CR) or Partial Response (PR) on CT, maintained for ≥ 12 weeks per RECIST 1.1
  • Treatment continuation: not meeting criteria above