RecruitingPhase 2NCT07615348

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

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

Sponsor

Jinling Hospital, China

Enrollment

75 participants

Start Date

Jun 16, 2026

Study Type

INTERVENTIONAL

Conditions

Metastatic Clear Cell Renal Cell Carcinoma

Summary

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.

Eligibility

Min Age: 18 Years

Inclusion Criteria23

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

Exclusion Criteria17

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

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Interventions

DRUGPD-1/PD-L1 ICI + VEGFR-TKI

All participants will receive first-line PD-1/PD-L1 inhibitor + VEGFR-TKI combination therapy for 12 months (±1 month).

OTHERTreatment pause

Patients who achieve the predefined criteria after 12 months of treatment will discontinue both drugs and enter a closely monitored treatment holiday. Upon radiographic or clinical progression, the previous systemic therapy will be reintroduced according to the protocol and investigator's discretion.