A Preliminary Efficacy of SNA028 in Patients With Advanced Colorectal Cancer Positive for GPA33

A Single-center, Open-label, Non-randomized Clinical Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of SNA028 in Patients With Advanced Colorectal Cancer Positive for GPA33

This clinical trial is a single-center, open-label, non-randomized first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics, radiation dosimetry, and preliminary efficacy of SNA028 (which is a two-step radioactivity pretargeting agents conducted by GPA33-CC and 177Lu-SmartD2) in patients with GPA33-positive colorectal cancer who have experienced disease progression/recurrence following prior standard therapy.

Study Overview

• Status: Not yet recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: GPA33-CC；177Lu-SmartD2

Detailed Description

The trial is planned to explore three main topics: 1.the dose of GPA33-CC. 2. the intervation between administration of GPA33-CC Inervation and 177Lu-SmartD2. 3.the mass dose of SmartD2.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Dong Dai, Doctor; Phone Number: 0512-23340123 0512-23340123; Email: 1014481959@qq.com

Study Locations

• China
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300000
      • Tianjin Medical University Cancer Institute and Hospital

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 colorectal cancer diagnosed by histopathology or cytology and experiencing imaging progression/recurrence after standard treatment;
6. According to RECIST 1.1 definition, there must be at least one measurable lesion;
7. Toxicity caused by previous treatment must be restored to ≤ level 2 (CTCAE v6.0) or to a stable state evaluated by the researcher (excluding hair loss and pigmentation);
8. Having sufficient organ function, defined as follows:

1) Bone marrow:

• White blood cell count 3.0~10.0 × 10^9/L
• Absolute neutrophil count 1.5~7.0 × 10^9/L
• Platelets 75~300 × 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 9. 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. Poor nutritional status and inability to tolerate the test subjects;
2. Individuals who have previously been allergic to SNA028 components or their analogues;
3. Patients who have received therapeutic drugs and radiation therapy labeled with 177Lu and other radioactive isotopes 4 weeks before SNA028 treatment;
4. Patients who have received other experimental anti-tumor drug treatments 4 weeks before SNA028 treatment;
5. Patients who received anti-GPA33 antibody treatment 4 weeks before SNA028 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. Diagnosed with other malignant tumors that may alter life expectancy or interfere with disease assessment;
9. Pregnant or lactating women;
10. 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

7

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dose group 1; GPA33-CC protein dosage 0.3mg/kg The interval is 7d and the mass dose of SmartD2 is 60nmol	Drug: GPA33-CC；177Lu-SmartD2; SNA028 is a two-step radioimmunotherapy, delivered as two separate products GPA33-CC and 177Lu-SmartD2, both will be administered as an IV infusion.
Experimental: Dose group 2; GPA33-CC protein dosage 1mg/kg. The interval is 7d and the mass dose of SmartD2 is 60nmol	Drug: GPA33-CC；177Lu-SmartD2; SNA028 is a two-step radioimmunotherapy, delivered as two separate products GPA33-CC and 177Lu-SmartD2, both will be administered as an IV infusion.
Experimental: Dose group 3; GPA33-CC protein dosage 3mg/kg. The interval is 7d and the mass dose of SmartD2 is 60nmol	Drug: GPA33-CC；177Lu-SmartD2; SNA028 is a two-step radioimmunotherapy, delivered as two separate products GPA33-CC and 177Lu-SmartD2, both will be administered as an IV infusion.
Experimental: Dose group 4; The interval is 3d. The mass dose of SmartD2 is 60nmol with optimal GPA33-CC protein dosage	Drug: GPA33-CC；177Lu-SmartD2; SNA028 is a two-step radioimmunotherapy, delivered as two separate products GPA33-CC and 177Lu-SmartD2, both will be administered as an IV infusion.
Experimental: Dose group 5; The interval is 5d. The mass dose of SmartD2 is 60nmol with optimal GPA33-CC protein dosage	Drug: GPA33-CC；177Lu-SmartD2; SNA028 is a two-step radioimmunotherapy, delivered as two separate products GPA33-CC and 177Lu-SmartD2, both will be administered as an IV infusion.
Experimental: Dose group 6; The mass dose of SmartD2 is 120nmol with optimal GPA33-CC protein dosage and interval.	Drug: GPA33-CC；177Lu-SmartD2; SNA028 is a two-step radioimmunotherapy, delivered as two separate products GPA33-CC and 177Lu-SmartD2, both will be administered as an IV infusion.
Experimental: Dose group 7; The mass dose of SmartD2 is 200nmol with optimal GPA33-CC protein dosage and interval.	Drug: GPA33-CC；177Lu-SmartD2; SNA028 is a two-step radioimmunotherapy, delivered as two separate products GPA33-CC and 177Lu-SmartD2, both will be administered as an IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the safety and tolerability of SNA028 in patients with advanced colorectal cancer.	Occurrence of AE/SAE after administration	3 weeks
To evaluate the safety and tolerability of SNA028 in patients with advanced colorectal cancer.	Occurrence of abnormal Laboratory tests after administration	3 weeks
To evaluate the safety and tolerability of SNA028 in patients with advanced colorectal cancer.	Occurrence of abnormal Vital signs after administration	3 weeks
To evaluate the safety and tolerability of SNA028 in patients with advanced colorectal cancer.	Occurrence of abnormal Physical examination after administration	3 weeks
To evaluate the safety and tolerability of SNA028 in patients with advanced colorectal cancer.	Occurrence of abnormal ECG after administration	3 weeks
To evaluate the pharmacokinetic of the GPA33-CC protein	Peak plasma concentration (Cmax) of the GPA33-CC	up to 1 week
To evaluate the pharmacokinetic of the GPA33-CC protein	half-life (t1/2) of the GPA33-CC	up to 1 week
To evaluate the pharmacokinetic of the GPA33-CC protein	Area under the concentration-time curve (AUC) of the GPA33-CC	up to 1 week
To evaluate the radiological characteristics 177Lu-SmartD2.	Rradiation doses in whole blood and serum measured using a gamma counter radiological characteristics 177Lu-SmartD2 will be performed.	up to 1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the biodistribution of SNA028	Absorbed dose in major organs throughout the body (red bone marrow, kidneys, liver, intestines, etc.)	up to 2 weeks
To evaluate the biodistribution of SNA028	Major organ and tumour standardised uptake (SUVmax and SUVmean)	up to 2 weeks
To evaluate the biodistribution of SNA028	The retention time of major organs and tumor.	up to 2 weeks
To evaluate the biodistribution of SNA028	The tumour-to-background ratio (TBR) of SUV	up to 2 weeks
Assessment of the immunogenicity of GPA33-CC	Occurance of positive immunogenicity	4 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessing tumour response according to RECIST1.1	The ORR of tumor	every 6 weeks up to 2 years
Assessing tumour response according to RECIST1.1	The DCR of tumors.	Every 6 weeks up to 2 years
Assessing tumour response according to RECIST1.1	The DOR of tumors.	every 6 weeks up to 2 years
Explore the PFS of subjects	PFS according to the RECIST1.1	2 years
To evaluate the correlation between the clinical efficacy of SNA028 and GPA33 expression	the correlation between overall response and Immunohistochemistry expression of GPA33	up to 2 years

Collaborators and Investigators

• Sponsor: SmartNuclide Biopharma
• Collaborators: Tianjin Medical University Cancer Institute and Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: April 17, 2026
• First Submitted That Met QC Criteria: May 12, 2026
• First Posted (Actual): May 15, 2026

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 12, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Colorectal cancer; 177Lu; Radiopharmaceuticals; GPA33
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms
• Other Study ID Numbers: SNA028-202601

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No