Colorectal Cancer
Conditions
Keywords
Colorectal cancer, GPA33, Radiopharmaceuticals, 177Lu
Brief 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.
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.
Interventions
DRUGGPA33-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.
Sponsors
SmartNuclide Biopharma
Tianjin Medical University Cancer Institute and Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 pharmacokinetic of the GPA33-CC protein | up to 1 week | Peak plasma concentration (Cmax) 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| To evaluate the biodistribution of SNA028 | up to 2 weeks | Absorbed dose in major organs throughout the body (red bone marrow, kidneys, liver, intestines, etc.) |
| Assessment of the immunogenicity of GPA33-CC | 4 weeks | Occurance of positive immunogenicity |
Countries
China
Contacts
CONTACTDong Dai, Doctor
Outcome results
None listed