A IIT Study of 177Lu-DOTA-SNA040

A Clinical Study Evaluating the Safety, Tolerability, Biodistribution, Dose Determination, and Preliminary Efficacy of ¹⁷⁷Lu-DOTA-SNA040 in Patients With Claudin 18.2-positive Advanced Solid Tumors

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors (Such as Gastric Cancer); Advanced Solid Tumors (Such as Adenocarcinoma at the Gastroesophageal Junction); Advanced Solid Tumors (Such as Pancreatic Cancer); Advanced Solid Tumors (Such as Cholangiocarcinoma)
• Intervention / Treatment: Drug: 177Lu-DOTA-SNA040

Detailed Description

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
• Enrollment (Estimated): 12
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: shaoli song, doctor; Phone Number: 0512-67229125; Email: mengru.wu@smartnucl.com

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200000
      • Recruiting
      • Fudan University Shanghai Cancer Center
      • Contact: Shaoli Song, PhD; Email: shaoli-song@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age range of 18 to 75 years old (including boundary values);
2. Individuals with behavioral capacity who voluntarily participate in this clinical study and sign an informed consent form (ICF);
3. Individuals with ECOG scores ranging from 0 to 1 (see Appendix 1 for details);
4. Life expectancy>6 months;
5. Patients with advanced solid tumors confirmed by histopathology or cytology (such as gastric cancer or adenocarcinoma at the gastroesophageal junction, pancreatic cancer, and cholangiocarcinoma) and confirmed by the investigator, who fail to receive first-line treatment or have disease progression; According to RECIST 1.1 definition, there must be at least one measurable lesion;

7. At least one lesion must be immunohistochemistry positive for Claudin18.2 (≥ 20% of tumor cells have Claudin18.2 immunohistochemistry membrane staining intensity ≥ 2+); Before the first administration of 177Lu-DOTA-SNA040 treatment, the toxicity caused by previous treatments must be restored to ≤ level 2 (CTCAE V5.0) or a stable state evaluated by the researcher (excluding hair loss and pigmentation); 177Lu DOTA-SNA040 has sufficient organ function one week before treatment, defined as follows:

1. Bone marrow:

   White blood cell count range from 3.0 to 10.0 × 10^9/L Absolute neutrophil count range from 1.5 to 7.0 × 10^9/L Platelets range from 75 to 300 × 10^9/L Hemoglobin ≥ 90g/L

2. Liver:

   Total bilirubin ≤ 2.5 x upper limit of normal (ULN) Serum albumin>3.0 g/dL Alanine aminotransferase and aspartate aminotransferase ≤ 3 × ULN or liver metastasis patients ≤ 5 × ULN

3. Kidney:

   Serum/plasma creatinine ≤ 1.5 × ULN or creatinine clearance rate ≥ 60 mL/min (calculated using the Cockcroft Gault formula)

4. Coagulation function The international standardized ratio of prothrombin is less than 1.5 × ULN Prothrombin time<2 × ULN During the treatment with 177Lu-DOTA-SNA040, the best support/standard of care agreed upon by the researcher is allowed; 11. Patients and/or partners with fertility must use adequate contraceptive measures during the study period and within 6 months after the last administration of the study drug.

Exclusion Criteria:

1. The nutritional status is extremely poor, with a BMI of less than 18.5 during screening, and the subjects cannot tolerate the test;
2. Individuals who have previously been allergic to 177Lu DOTA-SNA040 or its analogues;
3. Patients who have received therapeutic drugs and radiation therapy labeled with 177Lu and other radioactive isotopes 4 weeks before treatment with 177Lu DOTA-SNA040;
4. 177Lu DOTA-SNA040 patients who received antibody conjugated drug (ADC) treatment 4 weeks before treatment;
5. Those who have received other experimental anti-tumor drug treatments 4 weeks before 177Lu DOTA-SNA040 treatment;
6. Individuals known to have central nervous system metastases and/or malignant meningitis;
7. Major comorbidities: including but not limited to New York Heart Association grade III or IV congestive heart failure, a history of congenital QT interval prolongation syndrome, active severe infections, or other major diseases that the researcher deems unsuitable for participation in the study;
8. Patients with obvious gastric bleeding and/or untreated gastric ulcers;
9. Diagnosed with other malignant tumors that may alter life expectancy or interfere with disease assessment;
10. Pregnant or lactating women;
11. The researcher believes that they are not suitable to participate in this clinical study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; 30~70mCi	Drug: 177Lu-DOTA-SNA040; 177Lu-DOTA-SNA040 administration
Experimental: Group 2; 100mCi	Drug: 177Lu-DOTA-SNA040; 177Lu-DOTA-SNA040 administration
Experimental: Group 3; 150mCi	Drug: 177Lu-DOTA-SNA040; 177Lu-DOTA-SNA040 administration
Experimental: Group 4; 200mCi	Drug: 177Lu-DOTA-SNA040; 177Lu-DOTA-SNA040 administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose-limiting toxicity(DLT) of the single dose	Occurance of DLT in the first cycle of each group	4 to 6weeks
The safety and tolerance of 177Lu-DOTA-SNA040	The occurance and stage of AE and SAE according to CTCAE	4 to 6 weeks
The safety and tolerance of 177Lu-DOTA-SNA040	The rates of abnormal laborotary tests after administration	4 to 6 weeks
The safety and tolerance of 177Lu-DOTA-SNA040	The rates of abnormal vital signs after administration	4 to 6 weeks
The safety and tolerance of 177Lu-DOTA-SNA040	The rates of abnormal physical examination after administration	4 to 6 weeks
The safety and tolerance of 177Lu-DOTA-SNA040	The rates of abnormal 12-lead ECG after administration	4 to 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Explore the PFS of subjects	PFS according to the RECIST1.1	2 years
The biodistribution of SNA040	Absorbed dose in major organs throughout the body (red bone marrow, kidneys, liver, intestines, etc.)	1 week
The tumor uptake of SNA040	SUVmax and SUVmean of tumor	1 week
The tumor uptake of SNA040	The retention time of tumor	1 week
The tumor uptake of SNA040	The ID% of tumor	1 week
To evaluate the radiological characteristics 177Lu-DOTA-SNA040	Rradiation doses in whole blood, serum, urine measured using a gamma counter	1 week
The pharmacokinetic of the SNA040 protein	Peak plasma concentration (Cmax) of the SNA040	1 week
The pharmacokinetic of the SNA040 protein	Area under the concentration-time curve (AUC) of the SNA040	1 week
The pharmacokinetic of the SNA040 protein	Clearance (CL) of the SNA040	1 week
Assessment of the immunogenicity of SNA040	Occurance of positive immunogenicity test	1 week
Assessing tumour response according to RECIST1.1	The DCR of tumors	4 to 6 weeks
Assessing tumour response according to RECIST1.1	The ORR of tumors	4 to 6 weeks
Assessing tumour response according to RECIST1.1	The DOR of tumors	4 to 6 weeks
Explore the OS of subjects	Overall survival (OS) according to the RECIST1.1	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	2 years

Collaborators and Investigators

• Sponsor: SmartNuclide Biopharma

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2025
• Primary Completion (Actual): November 24, 2025
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: November 4, 2025
• First Submitted That Met QC Criteria: May 12, 2026
• First Posted (Actual): May 19, 2026

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Claudin18.2; 177Lu-DOTA-SNA040
• Other Study ID Numbers: SNA040-202501

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No