Safety and Tolerability Study of 68Ga/177Lu-BRP-020063 in Advanced Solid Tumors

A Study Evaluating the Safety, Pharmacokinetics, and Radiation Dosimetry of 68Ga/177Lu-BRP-020063 in Patients With Advanced Metastatic Solid Tumors.

This study is an open-label, single-arm, interventional clinical trial designed to investigate the safety of ⁶⁸Ga/¹⁷⁷Lu-BRP-020063 in patients with advanced metastatic solid tumors; to evaluate the pharmacokinetics, biodistribution, and radiation dosimetry of ¹⁷⁷Lu-BRP-020063 in patients with metastatic solid tumors; and to preliminarily explore its therapeutic efficacy. The study plans to enroll 10 patients to receive ⁶⁸Ga-BRP-020063 PET/CT imaging, among whom 5 patients positive for ⁶⁸Ga-BRP-020063 will be selected to receive a low dose of ¹⁷⁷Lu-BRP-020063. The results of this study will provide a basis for the design of subsequent studies involving higher doses of ¹⁷⁷Lu-BRP-020063.

Inclusion Criteria:

1. Age ≥ 18 years, regardless of gender;

2. Patients with a confirmed diagnosis of advanced metastatic solid tumor (preferably urothelial carcinoma, followed by breast cancer);

3. Willing to provide archived or freshly biopsied tumor tissue specimens (recommended within the past 2 years);

4. Performance status (ECOG) score of 0-1;

5. Adequate organ function:

   • Complete Blood Count: White blood cell count ≥ 3.0 × 10⁹/L, neutrophil count ≥ 1.5 × 10⁹/L, hemoglobin ≥ 90 g/L, platelet count ≥ 75 × 10⁹/L;
   • Liver function: Total bilirubin ≤ 2.5 × ULN, alanine aminotransferase ≤ 3 × ULN, aspartate aminotransferase ≤ 3 × ULN;
   • Renal function: Creatinine clearance ≥ 50 mL/min (Cockcroft-Gault formula);
   • Coagulation function: Prothrombin time ≤ 1.5 × ULN, activated partial thromboplastin time ≤ 1.5 × ULN, international normalized ratio ≤ 1.5 × ULN;

6. Subjects of childbearing potential must voluntarily adopt effective contraception during the treatment period and for 6 months after the last dose of the investigational drug (for females);

7. Willing to participate in this trial and sign an informed consent form.

Exclusion Criteria:

1. Previous treatment with Nectin-4-targeted drugs (including clinical trials);

2. Inability to complete PET/CT or SPECT/CT examinations (including inability to lie flat, claustrophobia, radiophobia, etc.);

3. Participation in drug or device clinical studies within 4 weeks prior to the first dose;

4. Presence of severe or uncontrolled underlying diseases, including but not limited to:

   1. NYHA Class II or higher congestive heart failure, or severe arrhythmia requiring medication;
   2. Severe cardiovascular/cerebrovascular or valvular diseases;
   3. Poorly controlled diabetes or hypertension;

5. Inability to tolerate intravenous administration or difficulty with venipuncture (e.g., history of needle or blood phobia);

6. Active infection within 4 weeks prior to the first dose;

7. Women who are planning pregnancy, currently pregnant, or breastfeeding;

8. Allergy to radioactive rays or other severe allergic history;

9. History of neurological metastasis with associated symptoms;

10. Concurrent other malignancies;

11. Undergone general anesthesia surgery within 4 weeks prior to the first dose;

12. Other conditions deemed by the investigator as unsuitable for inclusion in the clinical study.