China-based Simcere Zaiming Pharmaceutical Co., Ltd., the oncology subsidiary of Simcere Pharmaceutical Group Limited (HKEX: 2096), has disclosed fuller clinical development plans for SIM0532, an oral pan-RAS inhibitor that entered first-in-human development in May 2026. A newly posted Phase I trial record shows Simcere plans dose-expansion cohorts in pancreatic cancer, RAS-mutant non-small cell lung cancer (NSCLC) and other RAS-mutant solid tumors, placing the program in a mechanistic class now clinically validated by Revolution Medicines' daraxonrasib.
Simcere announced the first patient dosing in May, with treatment initiated at Fudan University Shanghai Cancer Center. The Phase I study (NCT07749703), posted to ClinicalTrials.gov on August 6, is an open-label, multicenter trial expected to enroll up to 346 adults. Part 1 uses Bayesian Optimal Interval (BOIN) dose escalation to establish a recommended dose, followed by tumor-specific expansion cohorts evaluating preliminary efficacy, including objective response rate (ORR).
SIM0532 uses a cyclophilin A (CypA)-mediated tri-complex approach to inhibit active RAS. The molecule first binds CypA non-covalently, with the resulting complex engaging GTP-bound RAS to form a ternary complex that sterically blocks interactions with downstream effectors. Unlike covalent inhibitors directed at individual KRAS mutations, SIM0532 is designed to target the active state of both mutant and wild-type RAS proteins across the KRAS, NRAS and HRAS families. Simcere has reported preclinical activity against both RAS-mutant tumor cells and cells with amplified wild-type KRAS, although no human efficacy data have yet been disclosed.
The approach closely parallels the RAS(ON) multi-selective strategy pioneered clinically by Revolution Medicines' daraxonrasib (RMC-6236), substantially raising the benchmark SIM0532 will eventually face. In the 500-patient Phase III RASolute 302 study published in the New England Journal of Medicine in May, daraxonrasib extended median overall survival to 13.2 months from 6.6 months with chemotherapy among previously treated metastatic pancreatic ductal adenocarcinoma patients with RAS G12 mutations (HR=0.40; p<0.001). Median progression-free survival was 7.3 versus 3.5 months (HR=0.45; p<0.001).
Those results provide randomized clinical validation for targeting active RAS through a CypA-mediated tri-complex mechanism, shifting the question for newer entrants such as SIM0532 from whether the approach can work in humans toward whether individual molecules can differentiate on RAS coverage, antitumor activity, tolerability or activity following earlier targeted treatment. Simcere has not disclosed structural or head-to-head pharmacological comparisons between SIM0532 and daraxonrasib.