Solid Cancers
Conditions
Brief summary
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.
Interventions
DRUGJY016
0.08μg/kg\~30μg/kg,QW
Sponsors
Biotech Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MTD | from baseline up to 4 weeks | The Maximum Tolerated Dose (MTD) is defined as the highest dose level of a drug or treatment that does not cause unacceptable side effects (Dose-Limiting Toxicities) in a specified number of patients during a 4-weeks treatment period. |
| Incidence of AEs | through study completion, an average of 1 year | Incidence of Adverse Events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | from baseline up to 4 weeks | Maximum Plasma Concentration |
| ORR | From date of enrollment until the date of first documented progression, assessed up to 24 months | The objective response rate(ORR) is defined as the sum of the proportions of patients achieving a Complete Response (CR) and a Partial Response (PR). |
Outcome results
None listed