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.
Study summary
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.
Eligibility
Sex
ALL
Min age
18 Years
Max age
75 Years
Healthy volunteers
No
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.
Primary outcome measure(s)
To evaluate the safety and tolerability of SNA028 in patients with advanced colorectal cancer. — 3 weeks Occurrence of AE/SAE after administration
To evaluate the safety and tolerability of SNA028 in patients with advanced colorectal cancer. — 3 weeks Occurrence of abnormal Laboratory tests after administration
To evaluate the safety and tolerability of SNA028 in patients with advanced colorectal cancer. — 3 weeks Occurrence of abnormal Vital signs after administration
To evaluate the safety and tolerability of SNA028 in patients with advanced colorectal cancer. — 3 weeks Occurrence of abnormal Physical examination after administration
To evaluate the safety and tolerability of SNA028 in patients with advanced colorectal cancer. — 3 weeks Occurrence of abnormal ECG after administration
To evaluate the pharmacokinetic of the GPA33-CC protein — up to 1 week Peak plasma concentration (Cmax) of the GPA33-CC
To evaluate the pharmacokinetic of the GPA33-CC protein — up to 1 week half-life (t1/2) of the GPA33-CC
To evaluate the pharmacokinetic of the GPA33-CC protein — up to 1 week Area under the concentration-time curve (AUC) of the GPA33-CC
To evaluate the radiological characteristics 177Lu-SmartD2. — up to 1 week Rradiation doses in whole blood and serum measured using a gamma counter radiological characteristics 177Lu-SmartD2 will be performed.
Trial sites (1)
Facility
City
Region
Status
Tianjin Medical University Cancer Institute and Hospital
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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