JY016 Injection in Patients With Advanced Solid Tumors Expressing EGFR

A Phase I/II Clinical Study on the Safety, Pharmacokinetic Characteristics and Preliminary Efficacy of JY016 Injection in Patients With Advanced Solid Tumors Expressing EGFR

This study is a single-arm, open-label, multi-center Phase I/II clinical trial, consisting of Part A: the Phase I dose escalation stage, and Part B: the Phase II expansion stage. The objective of the Phase I dose escalation stage is to evaluate the safety, pharmacokinetic characteristics, and preliminary efficacy of JY016 injection in patients with advanced solid tumors expressing EGFR (immunohistochemistry 1+, 2+, or 3+). In the Phase II stage, the efficacy of JY016 in pancreatic cancer, non-small cell lung cancer, esophageal cancer, colorectal cancer, and squamous cell carcinoma of the head and neck with EGFR expression will be further evaluated.

Inclusion Criteria:

• 1. Age ≥ 18 years and ≤ 75 years;
• 2. Tumor diagnosis and previous anti-tumor treatment: Phase I dose escalation stage: Subjects with advanced solid tumors with EGFR expression (immunohistochemistry 1+, 2+ or 3+) who have undergone standard treatment failure, or lack effective treatment options, or are unable to tolerate standard treatment, diagnosed by histological or cytological methods; Phase II expansion stage: Several tumor types with confirmed EGFR expression (initially determined as immunohistochemistry 1+, 2+ or 3+, and can be adjusted based on the exploratory results of EGFR expression in the dose escalation stage) confirmed by the central laboratory.
• 3. ECOG physical condition score is 0-1 point;
• 4. Expected survival exceeds 12 weeks;
• 5. The bone marrow reserve and organ function levels must meet the following requirements 4 weeks before the first administration:(1) Blood routine: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; platelet count ≥ 100 × 109/L; hemoglobin ≥ 90 g/L; (no blood transfusion or hematopoietic stimulating factor treatment within 14 days before the first administration);(2) Liver and kidney function: serum total bilirubin (TBIL) ≤ 1.5 × ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN; if there is liver metastasis, ALT and AST ≤ 5 × ULN; creatinine clearance rate ≥ 50 mL/min (using the Cockcroft-Gault formula) or serum creatinine ≤ 1.5 × ULN;(3) Coagulation function: activated partial thromboplastin time (APTT) ≤ 1.5 × upper limit of normal; international normalized ratio (INR) ≤ 1.5 × ULN;(4) Cardiac function: cardiac ultrasound examination, left ventricular ejection fraction ≥ 50%; QT interval (QTcF) ≤ 450 milliseconds.
• 6. At least one measurable lesion defined by RECIST v1.1 must exist at the baseline period;
• 7. Reproductive-capable subjects (male and female) must agree to use reliable contraceptive methods (hormonal or barrier methods or abstinence) with their partners during the trial period and for at least 3 months after the last administration; for pregnant women of childbearing age, a negative blood pregnancy test must be obtained within 14 days before the first use of the trial drug.
• 8.I have fully understood this study and voluntarily signed the informed consent form, willing and able to follow the research procedures.

Exclusion Criteria:

• 1. The time interval between the last anti-tumor treatment and the first administration: for cytotoxic drugs and small molecule targeted drugs, ≤ 3 weeks; for large molecule monoclonal antibodies, ≤ 4 weeks; for radiotherapy (except for local radiotherapy for relieving pain) ≤ 4 weeks; for traditional Chinese medicine with anti-tumor indications approved by NMPA, ≤ 2 weeks;
• 2. Known to be allergic to injectable JY016 or any of its excipient components; or having a history of allergy to drugs containing monoclonal components; other drug-induced liver toxicity or allergy history; or having a specific allergic reaction history (asthma, rubella, eczematous dermatitis); the subjects who have undergone previous anti-tumor treatment with central nervous system metastasis cancer, cancerous meningitis, or other central nervous system diseases or abnormalities;
• 3. Have received targeted CD3 drug treatment before;
• 4. Known to have central nervous system metastatic cancer, cancerous meningitis, or other central nervous system diseases or abnormalities;
• 5. Human immunodeficiency virus (HIV) antibody positive, syphilis antibody positive or having other acquired or congenital immune deficiency diseases; active hepatitis C, antibody positive and HCV RNA test positive; active hepatitis B, for HBsAg positive, HBV DNA needs to be detected, and HBV DNA is higher than the upper limit of the normal value;
• 6. Have received any anti-tumor treatment that was effective through T-cell recruitment therapy before, including but not limited to CAR-T and other in vitro cell therapies, CD3+ monoclonal antibodies, CD3+ dual antibodies, etc.;
• 7. Have had a subject who experienced cytokine release syndrome (CRS) after any treatment;
• 8. Have had anti-tumor treatment-related toxicity that has not been relieved to grade 1 or below (CTCAE v5.0) (excluding alopecia, pigmentation, and other toxicities determined by the investigator not affecting the safety of the study drug);
• 9. Have other malignant tumors (excluding skin basal cell carcinoma and carcinoma in situ that underwent radical treatment and no disease recurrence within 5 years before screening);
• 10. Have used other clinical trial test drugs within 4 weeks before the first administration of the test drug;
• 11. Have used live virus vaccines within 4 weeks before the first administration of the test drug or during the expected study period, and within 4 weeks after the expected cessation of the study treatment;
• 12. Have had active or requiring treatment bacterial, viral or fungal infections within 4 weeks before the first administration of the test drug;
• 13. History of active tuberculosis;
• 14. Have received allogeneic hematopoietic stem cell transplantation or solid organ transplantation;
• 15. Have active autoimmune diseases (including but not limited to immune-related myocarditis, immune-related pneumonia, myasthenia gravis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, Wegener's granulomatosis, multiple sclerosis, vasculitis or glomerulonephritis, etc.) within 1 year of receiving systemic treatment;
• 16. Have undergone major organ surgery (excluding biopsy and minimally invasive surgeries that have recovered well) or had significant trauma within 4 weeks before the first administration of the test drug, or need to undergo elective surgery during the study period;
• 17. Have had severe non-healing wounds/ulcers/fractures within 4 weeks before the first administration of the test drug;
• 18. Have a history of severe cardiovascular and cerebrovascular diseases, including but not limited to: 1) Severe cardiac rhythm or conduction abnormalities; 2) Congestive heart failure (NYHA classification ≥ III); 3) Acute coronary syndrome, aortic dissection, stroke or other grade 3 or above cardiovascular events within 6 months before the first administration;
• 19. Uncontrolled third space effusion (pleural effusion, pericardial effusion or abdominal effusion, etc.);
• 20. Known to have a history of drug abuse;
• 21. Pregnant or lactating women;
• 22.The investigator believes that the subject has other systemic diseases or other reasons that make them unsuitable to participate in this clinical study.