ANS-014004

Brief Summary: This is a Phase I, first-in-human, open-label, multi-center study designed to explore the safety, tolerability, PK, and anti-tumor antitumor activity of ANS014004 monotherapy in subjects with locally advanced or metastatic solid tumors.
* The study consists of two parts: a dose-escalation part (Part 1) and a dose-expansion part (Part 2). For each subject, the study will consist of a screening period (Day -28 to Day -1), a treatment period (until discontinuation of treatment) and a follow-up period (including safety follow-up and survival follow-up).
* During the Treatment Period, subjects will receive ANS014004 single-agent oral administration until the subject meets any treatment termination criteria.
1. The dose escalation phase (Part 1) will consist of a single-dose period and a multiple-dose period (28 days as one cycle). Subjects in the dose escalation phase will receive a single dose of ANS014004 on Day 1 of the single-dose period to obtain the complete PK profile of a single dose. There will be a 7-day washout period between the single-dose period and the multiple-dose period at the same dose level. If no dose-limiting toxicity (DLT) occurs within the 7-day washout period, subjects will start multiple-dose treatment on Day 8 (28 days per cycle), receiving ANS014004 once daily (QD) or twice daily (BID). Dose escalation will first be conducted in the QD dosing cohort. When the dose escalates to Cohort 5, dose escalation in the BID dosing cohort with the same daily dose will be conducted in parallel. For each group with the same daily dose of QD or BID cohorts, subjects will be enrolled in the QD cohort first, followed by the BID cohort, and then dose escalation of the next daily dose of QD or BID cohorts will be conducted. Both the QD and BID dosing cohorts will include a single-dose period and a multiple-dose period. Based on the safety, PK and preliminary efficacy data of the QD and BID cohorts, the dosing frequency and dose of the backfill cohort will be selected. Subjects in the backfill cohort will directly enter the multiple-dose period. The RP2D will be determined based on the comprehensive assessment of safety, PK and preliminary efficacy data from the dose escalation phase.
2. In the dose expansion portion (Part 2), subjects will receive oral administration of ANS014004 at the RP2D dose QD or BID in each treatment cycle (28 days per cycle). The end-of-treatment (EOT) visit will be conducted within 7 days after the last dose or when the investigator decides to discontinue treatment. During the study period, the investigator and the sponsor may discuss and decide whether to stop exploring certain dose cohorts or to add exploration of other doses or dosing regimens based on the safety, PK and preliminary efficacy data obtained previously.
All subjects will undergo imaging evaluations of their tumors every 8 weeks until disease progression is confirmed by the investigator, the subject begins new antitumor therapy, dies, is lost to follow-up, or withdraws from the study, whichever occurs first.

本研究旨在评估ANS014004联合EGFR-TKI用于EGFR突变阳性的局部晚期或转移性非小细胞肺癌（NSCLC）患者的安全性、初步疗效和药代动力学特征，以确定推荐剂量并进一步验证其治疗潜力。