Advanced Non-Small Cell Lung Cancer, Colorectal Cancer, and Esophageal Squamous Cell Carcinoma
Conditions
Interventions
Test group 1:Intra-tumor Injection 3× 10^6 cfu/m^2, 3× 10^7 cfu/m^2, 1x10^8 cfu/m^2
Test group 2:Intravenous Injection 3× 10^6 cfu/m^2, 3× 10^7 cfu/m^2, 1x10^8 cfu/m^2
Test group 3:Intravenous Injection 3.3 ×10^8 cfu/m^2, 1×10^9 cfu/m^2, 3.3×10^9cfu /m^2, 1×10^10cfu/m^2, 3.3×10^10cfu/m^2
Sponsors
Peking Union Medical College Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Volunteer to participate in clinical research; fully understand and be informed about this study and sign the ICF; willing to comply with and capable of completing all trial procedures; 2. Age: 18 to 75 years (inclusive), both males and females; 3. Enrolled subjects must have histologically or cytologically confirmed advanced or metastatic tumors (unresectable), with failure of standard treatment, intolerance to standard treatment, or refusal of standard treatment. The tumor types of enrolled subjects are limited to the following specific primary tumor types: non-small cell lung cancer, colorectal cancer, and esophageal squamous cell carcinoma; 4. Subjects with an ECOG performance status of 0 or 1; 5. According to RECIST v1.1 (solid tumors), subjects must have at least one measurable lesion [central nervous system (CNS) metastases alone are not accepted as measurable lesions]; 6. An expected survival period of at least 3 months; 7. If subjects have previously received anti-tumor therapy, they may only be enrolled after the toxic effects of previous treatments have recovered to baseline levels (except for residual alopecia effects) or to CTCAE v5.0 grade = 1.5 × 10?/L; b. Platelets >= 100 × 10?/L; c. Hemoglobin >= 9 g/dL; d. Serum creatinine 60 mL/min (estimated using the Cockcroft-Gault formula) for enrollment (Note: Creatinine clearance confirmation is only required when serum creatinine exceeds 1.5 × ULN); e. Serum total bilirubin <= 1.5 × ULN; f. Aspartate aminotransferase (AST), alanine aminotransferase (ALT) <= 2.5 × ULN; g. International normalized ratio (INR) or plasma prothrombin time (PT) <= 1.5 × ULN. h. Female subjects of childbearing potential or male subjects and their partners must agree to use effective contraception from the time of signing the ICF until 6 months after the last dose of the study drug.
Exclusion criteria
Exclusion criteria: 1. Known untreated CNS metastases, or subjects with leptomeningeal metastases, or subjects with unstable CNS metastases after treatment (symptoms within 4 weeks prior to initiation of study treatment, requiring hormonal therapy, or no radiographic evidence of lesion stability for more than 4 weeks); 2. Residual kanamycin antibiotic in this product, or subjects allergic to kanamycin antibiotics; 3. Subjects with active or a history of autoimmune disease that may recur (e.g., systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease, vasculitis, psoriasis, etc.) or at risk (e.g., having undergone organ transplantation requiring immunosuppressive therapy). However, subjects with the following conditions are allowed to proceed with further screening: type I diabetes, hypothyroidism requiring only hormone replacement therapy, skin diseases not requiring systemic treatment (e.g., vitiligo, psoriasis); 4. Subjects who required treatment with corticosteroids (prednisone > 10 mg/day or equivalent doses of other similar drugs) or other immunosuppressants for any condition within 14 days prior to study drug administration; 5. Other malignancies within 5 years prior to initiation of study treatment, except for radically treated basal cell carcinoma of the skin, carcinoma in situ of the breast, and carcinoma in situ of the cervix; 6. Systemic anti-tumor therapy within 28 days prior to initiation of study treatment, or less than 5 half-lives since the last anti-tumor treatment before the first dose of the investigational drug, whichever is shorter, including chemotherapy, immunotherapy, biological therapy (cancer vaccines, cytokines, or growth factors for cancer control), herbal or traditional Chinese medicine treatments; 7. Major surgery within 28 days prior to initiation of study treatment, or radical radiotherapy, or palliative radiotherapy within 14 days, or use of radiopharmaceuticals (strontium, samarium, etc.) within 56 days; 8. History of interstitial lung disease, chemical pneumonia, hypersensitivity pneumonitis, connective tissue disease-associated pneumonia, severe pulmonary fibrosis, acute lung diseases, etc. (except for localized interstitial pneumonia induced by radiotherapy), or uncontrolled allergic asthma; 9. Subjects with a known history of human immunodeficiency virus (HIV) infection; 10. Subjects with chronic active hepatitis B or active hepatitis C. Subjects positive for hepatitis B surface antigen (HBsAg) or hepatitis C virus (HCV) antibodies during screening must undergo further testing for HBV DNA titer and HCV RNA (above the lower limit of normal of the assay) to be eligible for enrollment; 11. Subjects with active tuberculosis; 12. Any active infection requiring systemic treatment within 2 weeks prior to initiation of study treatment; 13. History of solid organ transplantation; 14. History of immune-related adverse events (irAE) of grade >= 3 from previous immunotherapy; 15. Pregnant or breastfeeding women; men or women unwilling to use adequate contraception; women of childbearing potential must undergo a pregnancy test during screening; 16. Known history of alcoholism or drug abuse; 17. Significant cardiovascular diseases (e.g., congestive heart failure, unstable angina, atrial fibrillation, arrhythmias, etc.): history of acute myocardial infarction, unstable angina, stroke, or transient ischemic attack within 6 months prior to enrollment; congestive heart failure classified
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose limited toxicity, DLT;Maximum tolerated dose, MTD;Recommended Dose Expansion, RDE;Recommended Phase II Dose, RP2D; | — |
Secondary
| Measure | Time frame |
|---|---|
| pharmacokinetics; | — |
Countries
China
Contacts
Public ContactMengzhao Wang
Peking Union Medical College Hospital
Outcome results
None listed