A Phase I Study of SIM0532 in Adult Participants With Advanced Solid Tumors

Part 1 will be guided by the Bayesian Optimal Interval (BOIN) dose-escalation rule. In Part 2, patients with advanced pancreatic adenocarcinoma, RAS-mutant advanced non-small cell lung cancer (NSCLC) and other RAS-mutant advanced solid tumors.

• SIM0532 Tablets (Drug): SIM0532 Tablets

Primary outcomes

• Part 1: Dose-limiting toxicity (DLT) [Cycle 1 Day 1 (C1D1) to Cycle 1 Day 21 (C1D21) (Each cycle is 21 days)]
• Part 1: Safety: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) [From informed consent signing to 30 days after the last dose]
• Part 2: Incidence and severity of subjects with AEs/SAEs [From informed consent signing to 30 days after the last dose]
• Part 2: Objective response rate (ORR) [About 24 months.]

Secondary outcomes

• Maximum plasma concentration (Cmax) [About 24 months]
• Duration of response (DOR) [About 24 months]
• Disease control rate (DCR) [About 24 months]
• Time to response (TTR) [About 24 months]
• Overall survival (OS) [About 24 months]
• Progression-free survival (PFS) [About 24 months]

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* 1\. Signed the informed consent form prior to performing the specified procedures required by the study.
* 2\. Aged ≥18 years.
* 3\. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
* 4\. Expected survival ≥12 weeks.
* 5\. Laboratory test results indicating sufficient organ function.
* 6\. At least one measurable lesion per RECIST v1.1;

Exclusion Criteria:

* 1\. A history of other malignant tumors within 2 years.
* 2\. With symptomatic central nervous system (CNS) metastases.
* 3\. Gastrointestinal diseases that affect drug administration/absorption.
* 4\. Known psychiatric disorders or substance abuse that may interfere with the conduct of the study.
* 5\. Uncontrolled pleural effusion, pericardial effusion or ascites requiring drainage or medical intervention within 4 weeks.
* 6\. Any active infection requiring systemic treatment within 2 weeks.
* 7\. A history of non-infectious pneumonia requiring oral or intravenous steroid therapy for recovery, or interstitial lung disease (ILD) or severe obstructive pulmonary disease.
* 8\. Previous treatment with RAS-targeting therapies other than RAS (OFF) inhibitors.
* 9\. Failure to recover from adverse events (AEs) caused by previous antineoplastic therapy.
* 10\. Currently participating in or having participated in a study of other investigational drugs or devices within 4 weeks.
* 11\. Major surgery within 4 weeks.
* 12\. Previous antineoplastic therapy before the first dose of study treatment should have a certain wash-out period
* 13\. Vaccination with any live vaccine within 4 weeks.
* 14\. Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
* 15\. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection;
* 16\. A history of clinically significant cardiovascular disease.
* 17\. A history of allogeneic organ transplantation or graft-versus-host disease (GVHD).
* 18\. Known hypersensitivity to the study drug or any of its excipients.
* 19\. Participants who are pregnant or breastfeeding.