Evaluation of the I-phase Clinical Trial of 177Lu-HX02 Injection in Patients With Advanced Malignant Solid Tumors

Prior treatment

• Within the 3 months prior to the administration of 177Lu-HX02, the subject had received radiotherapy drugs, including but not limited to: lutetium-177, radium-223, etc.
• Within the 4 weeks prior to the administration of 177Lu-HX02, the subject had undergone major surgery, chemotherapy, biological therapy, immunotherapy, endocrine therapy (except hormone replacement), large molecule targeted therapy or off-label drug treatment. Within the 2 weeks prior to administration, the subject had received local palliative radiotherapy, traditional Chinese medicine with anti-tumor indications, small molecule targeted drugs.
• The medical history, computed tomography (CT) or magnetic resonance imaging (MRI) examination indicated the presence of central nervous system (CNS) metastatic lesions. Excluding: CNS metastatic lesions that have undergone radiotherapy or surgery, the subject did not use corticosteroids, anticonvulsants, or diuretics to control symptoms within 2 weeks prior to the first administration, the imaging indicated no progression or new onset of brain lesions, and there were no neurological symptoms.
• Currently has active infection and requires systemic anti-infection treatment (such as acute bacterial infection, tuberculosis, active hepatitis B/ C, active syphilis, etc.). Active hepatitis B is defined as: HBsAg or HBcAb test result is positive or exceeds the normal reference range, accompanied by hepatitis B virus titer > 2500 copies/mL or 500 IU/mL (excluding subjects who received anti-hepatitis B virus treatment for at least 14 days, HBV-DNA降至≤ 2500 copies/mL or 500 IU/mL， and agreed to continue treatment during the study period)； active hepatitis C is defined as： hepatitis C antibody positive or exceeds the normal reference range and HCV-RNA positive； syphilis-specific antibody positive； HIV antibody positive；
• Within the 5 years prior to the administration of 177Lu-HX02， the subject had any other active malignant tumors (excluding surgically resected and non-recurrent skin basal cell carcinoma， skin squamous cell carcinoma， superficial bladder cancer， local prostate cancer， in situ cervical cancer or other in situ cancers)；

Other illness

• Non-infectious pneumonia requiring hormone treatment and radiation pneumonitis， hemodynamic-altering thrombotic events， active bleeding events or other serious complications；
• Known to be allergic to the components of the study drug or its analogues；
• Suffering from claustrophobia or other conditions that prevent cooperation in PET/CT or SPECT/CT examinations；
• Patients with mental disorders such as depression， schizophrenia， delusion， hallucination or suicidal ideation；

Lab values

• Within 2 weeks prior to the first administration of the study drug, the subject had received blood transfusion, erythropoietin (EPO), granulocyte colony-stimulating factor (G-CSF), albumin infusion and renal replacement therapy.
• Suffering from severe cardiovascular diseases, including but not limited to the following conditions:
  • Within 6 months prior to administration, suffered from acute myocardial infarction, unstable angina pectoris, or received coronary angioplasty or stent;
  • New York Heart Association class II to IV congestive heart failure or left ventricular ejection fraction (LVEF) < 50% or within the lower limit of the normal range;
  • Uncontrolled hypertension (even with optimal treatment, with systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 100 mmHg);
  • Baseline electrocardiogram QTcF interval prolonged (> 480 ms);

Other

• Any person with difficulty in urination or urinary incontinence；
• Pregnant women；
• Other situations that the investigator considers the subject is not suitable to participate in this study.

• Have a thorough understanding of this study and have voluntarily signed the informed consent form;
• Age 18 to 75 years old, gender not restricted;
• ECOG score 0 to 1, able to tolerate PET/CT and SPECT/CT examinations;
• Expected survival period ≥ 6 months;
• Histologically or cytologically diagnosed as advanced malignant solid tumor;
• Previous standard treatment failed;
• 68Ga-HX01 PET/CT imaging positive. Defined as at least one lesion in the 68Ga-HX01 PET/CT imaging having SUVmax ≥ 3.0 or tumor-to-liver ratio (SUVmax/SUVmean) (T/L ratio) > 1;
• According to RECIST 1.1 standard, at least one measurable tumor lesion. For lesions that have received previous radiotherapy, the lesion can be included in the measurable lesion only when there is clear disease progression after radiotherapy;
• Toxicity of previous anti-tumor treatment (such as previous chemotherapy, radiotherapy, targeted therapy, immunotherapy, etc.) has recovered to ≤ grade 1 level (except for hair loss);
• The functional level of organs must meet the following requirements:
  • Bone marrow Neutrophil count ≥ 1.5×109/L and white blood cell count ≥ 2.5×109/L; Platelets ≥ 100×109/L; Hemoglobin ≥ 90 g/L;
  • Liver function Total bilirubin ≤ 1.5×ULN (for liver metastasis subjects, total bilirubin ≤ 2×ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < 3×ULN (for liver metastasis subjects, ALT and AST < 5×ULN); Albumin > 30 g/L;
  • Renal function Serum creatinine ≤ 1.5×ULN and creatinine clearance rate ≥ 50 mL/min;
  • Coagulation function International normalized ratio (INR) ≤ 2.0, activated partial thromboplastin time (APTT) ≤ 1.5×ULN. Exception: Subjects receiving warfarin anticoagulation therapy can have INR 2 to ≤ 3;
• Pregnant women of childbearing age need negative pregnancy test results. Subjects with reproductive capacity (and their partners) voluntarily use effective contraceptive methods during the treatment period and within 6 months after the last use of the investigational drug, such as condoms, oral or injectable contraceptives, etc.