Safety assessments and definition of DLT
non-DLTs, Cancer
ADVERSE EVENTS, ADVERSE EVENT, CANCER
DLT was defined as the occurrence of adverse events (AEs) that the investigator judged to be related to SYHA1813 within 28 days of the first dose during the dose-escalation period (Supplementary Table S1). The MTD was defined as the maximum dose for which the probability of a DLT was ≤ 33%.An accelerated titration design with one patient enrolled was utilized for the first two dose levels (5 and 15 mg). Then, a 3 + 3 dose-escalation design was employed starting from the third dose level (30 mg). If grade 3 or above adverse events (AEs, non-DLTs) occurred in one patient at the first two doses, two more patients were enrolled for further observation. If DLT was observed in one of the 3 patients, up to 3 more patients were enrolled at the same level. If 2 or more out of 3 to 6 patients experienced DLT at a dose level, the dose was decreased to the previous dose group. When decreasing to the previous dose group, if there were only 3 patients in the dose group, 3 more patients were added; if there were already 6 patients, the dose escalation ended, and the dose was defined as the MTD. Any patient who withdrew from the study before the completion of the DLT observation period due to a reason other than DLT was replaced. Dose de-escalation or reduction was permitted if safety re-evaluation was deemed necessary.Safety analyses were conducted for all patients who received at least one dose of SYHA1813. AEs were assessed throughout the study using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. The health status assessment of the patients included a physical examination (vital signs, weight, PS score, etc.), hematologic and biochemical profiling, routine urine and stool tests, and electrocardiogram assessment performed at screening and throughout the study.