This clinical trial is a single-center, open-label, non-randomized, first-in-human (FIH), dose-escalation study evaluating the safety, tolerability, and preliminary efficacy of 177Lu-DOTA-SNA040 in patients with advanced Claudin18.2-positive solid tumors (e.g., gastric cancer, gastroesophageal junction adenocarcinoma, pancreatic cancer, cholangiocarcinoma, etc.) who have disease progression following first-line therapy.
Eligible subjects should first undergo 68Ga-NODAGA-SNA014 PET/CT imaging. Patients with negative 68Ga-NODAGA-SNA014 tumor uptake will be discharged from the study after one week of follow-up for adverse events. Patients with positive 68Ga-NODAGA-SNA014 tumor uptake (SUVmax ≥10) will proceed to the subsequent 177Lu-DOTA-SNA040 dose escalation study (with at least a 2-day interval between 68Ga-NODAGA-SNA014 imaging and 177Lu-DOTA-SNA040 treatment). After completing the first cycle of dosing for DLT observation, subsequent 2-6 cycles of 177Lu-DOTA-SNA040 treatment may be administered. For dose group 1, the subsequent 2-6 cycles of 177Lu-DOTA-SNA040 dosing activity will be determined by the investigator, with the dose per cycle adjustable. For dose groups 2-4, the 177Lu-DOTA-SNA040 dosing activity will follow the fixed original dose (e.g., the first cycle dose for dose group 2 is 100 mCi, with subsequent 2-6 cycles fixed at 100 mCi).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
12
177Lu-DOTA-SNA040 administration
Fudan University Shanghai Cancer Center
Shanghai, Shanghai Municipality, China
RECRUITINGDose-limiting toxicity(DLT) of the single dose
Occurance of DLT in the first cycle of each group
Time frame: 4 to 6weeks
The safety and tolerance of 177Lu-DOTA-SNA040
The occurance and stage of AE and SAE according to CTCAE
Time frame: 4 to 6 weeks
The safety and tolerance of 177Lu-DOTA-SNA040
The rates of abnormal laborotary tests after administration
Time frame: 4 to 6 weeks
The safety and tolerance of 177Lu-DOTA-SNA040
The rates of abnormal vital signs after administration
Time frame: 4 to 6 weeks
The safety and tolerance of 177Lu-DOTA-SNA040
The rates of abnormal physical examination after administration
Time frame: 4 to 6 weeks
The safety and tolerance of 177Lu-DOTA-SNA040
The rates of abnormal 12-lead ECG after administration
Time frame: 4 to 6 weeks
The biodistribution of SNA040
Absorbed dose in major organs throughout the body (red bone marrow, kidneys, liver, intestines, etc.)
Time frame: 1 week
The tumor uptake of SNA040
SUVmax and SUVmean of tumor
Time frame: 1 week
The tumor uptake of SNA040
The retention time of tumor
Time frame: 1 week
The tumor uptake of SNA040
The ID% of tumor
Time frame: 1 week
To evaluate the radiological characteristics 177Lu-DOTA-SNA040
Rradiation doses in whole blood, serum, urine measured using a gamma counter
Time frame: 1 week
The pharmacokinetic of the SNA040 protein
Peak plasma concentration (Cmax) of the SNA040
Time frame: 1 week
The pharmacokinetic of the SNA040 protein
Area under the concentration-time curve (AUC) of the SNA040
Time frame: 1 week
The pharmacokinetic of the SNA040 protein
Clearance (CL) of the SNA040
Time frame: 1 week
Assessment of the immunogenicity of SNA040
Occurance of positive immunogenicity test
Time frame: 1 week
Assessing tumour response according to RECIST1.1
The DCR of tumors
Time frame: 4 to 6 weeks
Assessing tumour response according to RECIST1.1
The ORR of tumors
Time frame: 4 to 6 weeks
Assessing tumour response according to RECIST1.1
The DOR of tumors
Time frame: 4 to 6 weeks
Explore the PFS of subjects
PFS according to the RECIST1.1
Time frame: 2 years
Explore the OS of subjects
Overall survival (OS) according to the RECIST1.1
Time frame: 2 years
the correlation between the clinical efficacy of SNA040 and Claudin18.2 expression
the correlation between overall response and Immunohistochemistry expression of Claudin18.2
Time frame: 2 years
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