Iodine-refractory differentiated thyroid carcinoma, stage IV non-small cell lung cancer, breast cancer
Conditions
Interventions
Dose escalation phase(First stage):177Lu-D7ND injection
Dose expansion phase(Second stage):177Lu-D7ND injection
Sponsors
The First Affiliated Hospital of Xi'an Jiaotong University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Age above 18 years old, under 75 years old (including the critical value), gender is not limited; 2. Histologically or cytologically confirmed subjects with locally advanced, recurrent, or metastatic solid tumors that are inoperable and have failed standard treatment, including but not limited to thyroid cancer (DTC), lung cancer (NSCLC), and breast cancer, and have failed standard treatment, or currently have no standard treatment available, or are not available; 3. 68Ga-D7ND PET/CT imaging showed positive expression of FAP in all target lesions within 28 days before the first administration of the drug (positive expression of FAP was defined as that the lesion uptake was greater than or equal to the normal muscle tissue uptake of the psoas major muscle), and SUVmax of more than 50% of target lesions was >=10; 4. At least one measurable lesion is present. The lesion must be measured by enhanced CT or magnetic resonance imaging (MRI) according to RECIST v1.1: Measurable lesions were defined as non-lymphoid lesions with the longest single diameter >=10 mm, or lymph node lesions with a short diameter >=15 mm. Lesions after previous external radiotherapy or ablation can also be used as measurable target lesions if they have clearly progressed according to RECIST v1.1 and their longest diameter is >=10 mm. Bone metastases (including identifiable soft tissue components) are not measurable lesions; 5. Estimated survival time >=12 months; 6. ECOG physical status score 0-1; 7. Female subjects of childbearing age, male subjects and male subjects' partners agree to take effective contraceptive measures (such as abstinence, sterilization, contraceptives, injection of the contraceptive megestrol or subcutaneous implantation, etc.) during the corresponding period, the specific time requirements are as follows: Female subjects should use highly effective contraception during treatment and for 6 months after treatment; Male subjects should use highly effective contraception during treatment and for 90 days after treatment; The female partner of the male subject should use highly effective contraception during the male subject's treatment and for 90 days after treatment; 8. The subjects are informed, voluntarily participate and sign the informed consent. 1.Subjects with iodine-refractory differentiated thyroid cancer: 1. Histologically or cytologically confirmed DTC (including papillary carcinoma, follicular carcinoma, Hurthle cell carcinoma, and other variants); The tumor is locally advanced and/or distant, has lost indications for surgery or cannot be treated with external radiation therapy: Local advanced stage refers to T4 AnyN M0 in the TNM stage. Metastatic means AnyT AnyN M1 in TNM stage. 2.Subjects with iodine-refractory differentiated thyroid cancer: 2. The subject must have disease progression confirmed by imaging within 14 months prior to initiation of the therapeutic drug; 3.Subjects with iodine-refractory differentiated thyroid cancer: 3. Definition of radioiodine refractory: After detoxination, in the absence of exogenous iodine load interference, thyroid stimulating hormone (TSH) (>30 mU/L) stimulation state can be diagnosed as iodine-refractory thyroid cancer if any of the following conditions occur: All known DTC lesions did not take iodine. Disease progression occurs after treatment with 131 iodine, despite partial or total iodine supplementation. The progression was characterized by at least one of the following: elevated levels o
Exclusion criteria
Exclusion criteria: 1. Any target lesion was confirmed as FAP negative by 68Ga-D7ND PET/CT imaging; 2. A history of other malignancies, with the exception of the following conditions: malignant lesions have been treated with therapeutic measures and no known active lesions exist 5 or more years prior to initiation of the study drug, and the risk of recurrence is low as determined by the investigator; Adequately treated non-melanoma skin cancer or malignant lentigo with no evidence of disease progression; Adequately treated cervical cancer in situ with no evidence of progression; Prostatic intraepithelial tumor, no evidence of prostate cancer; Subjects with localized prostate cancer who have maintained normal prostate-specific antigen levels for more than 1 year after radical resection and/or radical radiotherapy may be included; 3. The adverse reactions of previous anti-tumor therapy have not returned to NCI-CTCAE v5.0 rating = 1.5 times the upper limit of the normal reference range (ULN), which is not applicable to subjects with known Gilbert disease; c. In the absence of liver metastasis, glutamic-pyruvic transaminase (ALT), glutamic-oxalic transaminase (AST) or alkaline phosphatase (ALP) >= 2.5 times ULN; ALT, AST or ALP >= 5x ULN during liver metastasis; d. Serum creatinine =1.5 times ULN or creatinine clearance = 2+ was detected by routine urine test or urine protein >= 1 g/24 h was detected quantitatively by 24-hour urine protein test, it was not allowed to be included in the group; f. International Standardized ratio (INR) >=1.5 or partially activated prothrombin time (APTT) >=1.5 times ULN. INR is only for subjects who are not receiving anticoagulant therapy; g. Serum potassium/magnesium ions beyond the normal range and clinically significant (whether
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetics and radiation dosimetry;Safety and tolerability;To determine the maximum tolerated dose of 177Lu-D7ND injection; | — |
Secondary
| Measure | Time frame |
|---|---|
| Curative effect; | — |
Countries
China
Contacts
Public ContactRui Gao
The First Affiliated Hospital of Xi'an Jiaotong University
Outcome results
None listed