An Open Label, Dose-escalation and Extension, Phase I Clinical Study on Evaluating Safety, Tolerability and Pharmacodynamics of Intravenous Administration of IDOV-SAFE in Patients with Advanced Malignant Solid Tumors Who Have Failed in Standard Treatment.
Subjects were Chinese patients with histologically or cytologically confirmed advanced malignant solid tumors (mainly focused on MSS type colon and rectal cancer) who had failed standard systemic therapy and were inoperable. The first stage was the dose escalation stage, which was divided into 4 dose groups according to the 3+3 dose escalation principle. One patient was enrolled in the first dose group, and 3-6 patients were enrolled in each of the latter three dose groups, with a total of 10-19 patients enrolled. The second stage is the security extension stage, which is selected by SMC 1-2 dose cohorts were expanded for safety and divided into three cohorts in total(IIA, IIB, IIC) to explore the safety of sequential or combined administration modes with immune targeted therapy. Each cohort included 6-12 subjects at different dose levels, and three cohorts could be carried out at the same time. The third stage is the dose expansion stage. According to the safety, PK and clinical data of the three cohorts in the second stage, 1-2 cohorts were selected by SMC for dose expansion. The sample size of each cohort was expanded to 20 cases on the original basis. The estimated ORR of the trial drug was 24%, and the ORR of the standard treatment was 5%. When the type I error was one-sided 0.025, and the power was 80%, the sample size was estimated by the normal approximation method. So each dose expansion phase A minimum of 20 subjects were required to be enrolled in the cohort.
‣ 1\. Be fully aware of this study and voluntarily sign ICF. 2. Age range from 18 to 70 years old at the time of screening, gender is not limited.
‣ 3\. At the time of screening, patients with advanced malignant digestive system tumors confirmed by histology or cytology, including MSS type colorectal cancer, bile duct cancer, stomach cancer, esophageal cancer, liver cancer, etc.
‣ 4\. At the time of screening, the disease has progressed after or during standard treatment; Subjects with advanced malignant digestive system tumors with no standard treatment currently available, intolerance to chemotherapy, or greater than or equal to progression after 2-line system therapy.
• Be fully aware of this study and voluntarily sign ICF.
• Age range from 18 to 70 years old at the time of screening, gender is not limited.
• At the time of screening, patients with advanced malignant digestive system tumors confirmed by histology or cytology, including MSS type colorectal cancer, bile duct cancer, stomach cancer, esophageal cancer, liver cancer, etc.
• At the time of screening, the disease has progressed after or during standard treatment; Subjects with advanced malignant digestive system tumors with no standard treatment currently available, intolerance to chemotherapy, or greater than or equal to progression after 2-line system therapy.
• When screening, the ECOG score of physical strength score is 0 or 1.
• Life expectancy assessed by the investigator at the time of screening was ≥3 months.
• Subjects had adequate organ function at baseline:
• a) Bone marrow function (no growth factor support therapy or component transfusion within 14 days prior to screening) : i. Neutrophil absolute value (ANC) ≥1.5×109/L; ii. Hemoglobin (HB) ≥90g/L; iii. Platelet count (PLT) ≥75×109/L; b) Liver function: i. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 1.5 times the upper limit of normal (ULN) (ALT and AST≤ 3 times ULN for liver metastasis or hepatocellular carcinoma); ii. Total blood bilirubin ≤ 1.5 ULN (in subjects with liver metastasis or hepatocellular carcinoma or Gilbert syndrome or familial benign nonbinding hyperbilirubinemia, the acceptable range of this indicator is ≤2.5 ULN); c) Renal function: serum creatinine ≤ 1.5x ULN or creatinine clearance ≥50mL/min;
• Fertile female subjects must have negative blood beta-HCG test results within 7 days prior to enrollment.
• Subjects must agree to use highly effective contraception for at least 90 days from the start of the ICF to the end of the study.
⁃ At least one measurable lesion according to RECIST v1.1 criteria, The target lesion had not been treated with radiotherapy or had definite radiographic progression after previous radiotherapy.