On May 21, 2026, Simcere Zaiming announced that SIM0532, a pan-RAS-targeted investigational anti-tumor drug independently developed by the company, has entered Phase I clinical development. The first patient was recently dosed at Fudan University Shanghai Cancer Center.
This multicenter, open-label Phase I study is jointly led by Professor Xianjun Yu of Fudan University Shanghai Cancer Center and Professor Shengxiang Ren of Shanghai Pulmonary Hospital affiliated with Tongji University. The trial plans to enroll approximately 346 patients with solid tumors and is designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary anti-tumor efficacy of SIM0532.
RAS proteins regulate key cellular processes including proliferation and differentiation. Mutations in RAS can lead to persistent pathway activation and drive tumorigenesis. The RAS family consists of KRAS, NRAS, and HRAS, among which KRAS mutations are the most prevalent. In Chinese patients, KRAS mutation rates are reported to be approximately 85% in pancreatic cancer, 55% in colorectal cancer, and 12.5% in lung cancer, according to literature reports.
SIM0532 is a novel oral small-molecule RAS inhibitor with a non-covalent mechanism of action that selectively targets both wild-type and mutant RAS proteins. The compound specifically targets the GTP-bound active state of RAS by binding intracellular cyclophilin A (CypA) to form a ternary complex. This mechanism sterically blocks the interaction between RAS and downstream effector proteins, thereby inhibiting oncogenic signaling pathways and suppressing tumor growth. Preclinical studies have demonstrated that SIM0532 exhibits potent anti-tumor activity in vitro against both RAS-mutant tumor cells and KRAS wild-type amplified tumor cells.