Advanced Malignant Solid Tumor of Digestive System Clinical Trial
Official title:
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 inoperable Chinese patients with histologically or cytologically confirmed advanced malignant solid tumors (mainly focusing on MSS type colorectal cancer) who had failed standard systemic therapy. In the first stage, each subject was given three doses on day 1, day 3 and day 5, and was divided into 4 dose groups, including 1 subject in the first dose group and 3-6 subjects in each of the last three dose groups. The second stage was the dose extension stage, with 2 dose groups, at least 10 subjects were enrolled in the selected group, and the administration method was the same as that of the first stage. There were about 20-60 cases in the two stages.
The therapeutic dose for mice was 1E8PFU, and the maximum starting dose for humans was 2.67E9 PFU based on the Guidelines for Estimating the Maximum Recommended Starting Dose for the First Clinical Trial of Healthy Adult Volunteers. Dose escalation phase: At this stage, we plan to enroll about 10-19 patients with advanced malignant solid tumors confirmed by histology or cytology after failure of standard treatment or without standard treatment in China for intravenous administration of IDOV-SAFETM. This stage was divided into two cohorts: Cohort 1: patients with MSS type colorectal cancer were included; Cohort 2: patients with digestive system tumors such as cholangiocarcinoma, gastric cancer, esophageal cancer, and liver cancer were included (about 6 to 13 subjects in cohort 1 and 4 to 6 subjects in cohort 2 were included preferentially, ensuring that 1 to 2 subjects for each tumor species were included). This phase consisted of four dose groups: 1E9 PFU, 3E10 PFU, 1E10 PFU and 3E10 PFU. The first dose group included 1 subject, and the other dose groups were increased by "3+3", with 3-6 subjects in each group. All subjects in each dose group may be progressively moved to the next dose group after completing a 28-day safety assessment. The dose escalation or setting may be adjusted as determined by the Safety Committee (SMC). Dose expansion phase: In the dose expansion stage, the previous dose or an intermediate dose of MTD and the subsequent clinical dosage to be used were selected to carry out the expansion test, and 1 to 2 tumor species were selected for expansion according to the efficacy of different tumor species in the dose escalation stage. Each dose level was extended to at least 10 subjects, with each patient receiving one course of treatment (21 days). Based on the preliminary clinical trial data, the number of injections and the interval time of administration can be adjusted during the dose expansion phase after the decision of the Safety Monitor Committee (SMC). Duration of treatment: In two phases, D22 began to enter a continuous treatment period. 3 weeks (21 days) was a course of treatment, and intravenous administration was performed on D1, 3, and 5 of each course. Safety-related tests are required for each course of treatment. Tumor efficacy was evaluated every 2 courses (every 6 weeks) according to RECIST1.1 and iRECIST criteria, and pharmacodynamic tests (including tumor markers, T cell subsets, cytokines, and viral load in tumor tissue, etc.) were performed regularly. During the continuous treatment period, when the subject meets the criteria of 9.1 subject end of treatment, the continuous treatment period will end and the subject will enter the long-term safety and survival follow-up period. Long-term safety and survival follow-up: Adverse events occurring throughout the study from the first dosing of each subject will be collected, and long-term safety and survival follow-up will continue up to 2 years after the last dosing (visits every 8 weeks until death or loss of follow-up, or the end date of survival follow-up). Prior to the initiation of a new antitumor therapy, the subjects were examined according to "6.8 Clinical Trial Schedule". After the subject has started a new anti-tumor therapy, a telephone visit can be made to confirm the subject's survival only. ;