Solid tumors
Conditions
Interventions
single agent escalation study:22-48 subjects are proposed to be enrolled in the single-agent escalation study and will receive A168 monotherapy. A total of 8 dose groups were designed. Accelerated tit
a 3 + 3 design was used in the subsequent dose groups of 6, 8, 10, 13, 16, 18 and 20 mg/kg, and 3-6 subjects were proposed to be included in each dose group. The specific sample size was increased or
a combination exploration study.:12-18 subjects with advanced gastric adenocarcinoma or gastroesophageal adenocarcinoma will be enrolled in the combination exploration study and treated with A168 inje
Sponsors
Zhongshan Hospital Affiliated to Fudan University
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: Cohort 1 study subjects must meet all of the following criteria for inclusion: 1. Age = 18 years, male or female; 2.Patients with histologically or cytologically confirmed locally advanced or metastatic solid tumors who have failed at least one line of standard of care or who have failed or refused standard of care, and have at least one evaluable lesion that meets the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; 3.Expected survival = 3 months using Eastern Cooperative Oncology Group (ECOG) scale score of 0 to 1 ; 4.Adequate organ and bone marrow function as defined below:Hematology: white blood cell count (WBC) = 4.0 × 10^9/L and < 12 × 10^9/L, or neutrophil count (Neu) = 1.5 × 10^9/L; platelet count (PLT) = 100 × 10^9/L; hemoglobin concentration = 9.0 g/dL;Liver function: lactate dehydrogenase (LDH) = 10 × ULN; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5 times the upper limit of normal (ULN), and ALT and AST = 5 × ULN for patients with liver cancer or liver metastases; total bilirubin (TB) = 1.5 × ULN, TB = 3 × ULN for patients with liver cancer, liver metastases, or Gilbert ’ s syndrome;Renal function: serum creatinine (Crea) = 1.5 × ULN or creatinine clearance (CLcr) = 50 mL/min (using the standard Cockcroft-Gault formula, see Attachment 6);Coagulation: international normalized ratio (INR), activated partial thromboplastin time (APTT), and prothrombin time (PT) = 1.5 × ULN; 5.Patients have a urine protein concentration = 1 + based on dipstick or routine urinalysis (UA) and are not accompanied by edema or serum albumin levels below the lower limit of the normal range (LLN). Alternatively, if the patient has a urine protein concentration = 2 +, the urine protein concentration in the 24-hour urine protein analysis must be < 1 g/24 h without edema or serum albumin below the LLN; 6.Patients who have previously used chemotherapeutic drugs should be discontinued for more than 4 weeks (mitomycin or nitrosoureas, which should be discontinued for more than 6 weeks) and recover from previous toxic reactions (= Grade 1 according to the criteria of CTC AE version 4.03, except alopecia); those who have received surgery, molecular targeted, or immunotherapy should be treated for more than 4 weeks, and those who have received palliative radiotherapy should be treated for more than 2 weeks, and their general physical condition has recovered; 7.No specialist treatment such as transfusion, blood products or blood cytokines such as granulocyte colony stimulating factor (G-CSF) within 2 weeks; 8.Subjects of childbearing potential (male or female) must use effective medical contraception during the study and for 3 months after the end of dosing; 9.With my consent and signed by me or his/her legal representative. Cohort 2 study subjects must meet all of the following criteria for inclusion: 1. Age = 18 years, male or female; 2.Patients with histologically or cytologically confirmed locally advanced or metastatic gastric adenocarcinoma or gastroesophageal adenocarcinoma who have failed only fluorouracils with or without platinum as first-line standard of care (at least 4 courses) and have at least one evaluable lesion that meets Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1; 3.Expected survival = 3 months using Eastern Cooperative Oncology Group (ECOG) scale score of 0 to 1 ; 4.Adequate organ and bon
Exclusion criteria
Exclusion criteria: Cohort 1 subjects who meet any of the following criteria will be excluded: 1) Subjects with a history of allergic diseases, serious drug allergies, and allergies to this product and excipients 2) Patients with brain malignancies, lymphomas, or other hematologic malignancies 3) Patients with clinically symptomatic uncontrolled brain metastases 4) Currently receiving other anti-tumor therapies 5) Patients with serious infections (including but not limited to progressive or active infections) (e.g., requiring intravenous antibiotics, antifungal or antiviral drugs, etc.) 6) Received previous therapy with a monoclonal antibody to VEGF or VEGFR Prior treatment with monoclonal antibodies to VEGF or VEGFR 7) Severe or unhealed trauma, ulceration, or fracture within 28 days prior to study entry 8) The patient experienced any Grade 3 or 4 gastrointestinal bleeding within 3 months prior to study entry 9) The patient had an abdominal wall fistula, gastrointestinal perforation, active or incurable postoperative bleeding complications or wound complications due to surgical procedures, or intra-abdominal abscesses within 6 months prior to randomization, or the patient had a history of poorly controlled or recurrent inflammatory bowel disease (including Crohn's disease or ulcerative colitis) 10) Patients are receiving long-term treatment with nonsteroidal anti-inflammatory drugs (NSAIDS; e.g. indomethacin, ibuprofen, naproxen, or similar; except Celebrex) or antiplatelet drugs (e.g., clopidogrel, ticlopidine, dipyridamole, or anagrel), anticoagulants (e.g., rivaroxaban, apixaban, etc.). However, aspirin (acetylsalicylic acid) at a dose of 325 mg/day or less is allowed 11) Patients with serious medical conditions, such as Grade II or higher cardiac dysfunction (NYHA criteria), ischemic heart disease (such as myocardial infarction or angina), congestive heart failure, poorly controlled diabetes mellitus (fasting blood glucose = 10 mmol/L), poorly controlled hypertension (systolic blood pressure = 140 mmHg and/or diastolic blood pressure = 90 mmHg), immune disease, acute pneumonia, interstitial pneumonia or pulmonary fibrosis, symptomatic pleural effusion or ascites requiring drainage 12) HIV;(HBV-DNA> 2000 IU/ml(> 104/ml));(HCV-RNA> 200 IU/ml(> 103/ml)) Known HIV seropositivity; or active hepatitis B (hepatitis B surface antigen positive and HBV-DNA > 2000 IU/ml (> 104 copies/ml)); or hepatitis C (hepatitis C virus antibody positive and HCV-RNA > 200 IU/ml (> 103 copies/ml)) 13) Presence of a clear neurological or psychiatric disorder (including dementia) that affects judgment or affects the collection of relevant information, or has previously been diagnosed with epilepsy 14) Symptomatic thyroid dysfunction requiring treatment 15) Patients with a clear history of alcohol or drug abuse 16) Pregnant or lactating women 17) Clinical Investigator who received other drugs within 1 month prior to the study 18) Other circumstances that, in the opinion of the investigator, are inappropriate for participation in this study. Subjects in Cohort 2 who meet any of the following criteria will be excluded: 1) Subjects with allergic diseases, a history of serious allergies to drugs, allergies to paclitaxel, and allergies to this product and excipients 2) Patients with brain malignancies, lymphomas, or other hematologic malignancies 3) Patients with clinically symptomatic uncontrolled brain metastases 4) Patients who have received prior paclitaxel-containing thera
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pharmacokinetic ;Immunogenicity;DLT;MTD; | — |
Countries
China
Contacts
Public ContactTianshu Liu
Zhongshan Hospital Fudan University
Outcome results
None listed