A Phase II Trial of CD70-Targeted Immuno-PET/CT-Directed Treatment Holiday for Metastatic Clear Cell Renal Cell Carcinoma With IMDC Favorable or Intermediate Risk
The purpose of this study is to evaluate the safety and feasibility of a treatment holiday strategy directed by CD70-targeted immuno-PET/CT in patients with metastatic clear cell renal cell carcinoma (mccRCC). Specifically, the study aims to assess whether patients who achieve both anatomical disease control and metabolic response after 12 months of first-line PD-1/PD-L1 ICI + VEGFR-TKI combination therapy can safely pause their treatment, improve quality of life without compromising therapeutic efficacy.
∙ 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