SY-5933

SY-5933 is a small molecule drug that specifically targets the KRAS G12C mutation, which is found in various types of cancer. It is being developed by Shouyao Holdings (Beijing) Co. Ltd. and is currently in Phase 1/2 clinical trials[1][2]. ## Mechanism of Action SY-5933 functions as a KRAS G12C inhibitor, targeting the specific G12C mutation in the KRAS protein. This mutation is particularly relevant in certain types of cancer, including non-small cell lung cancer (NSCLC), colorectal cancer, and pancreatic cancer[1][5]. By inhibiting the mutated KRAS G12C protein, SY-5933 aims to block downstream signaling pathways that drive tumor growth and survival. ## Clinical Development The drug is being evaluated in several clinical trials: 1. A Phase 1 study (NCT06006793) evaluating SY-5933 as monotherapy in patients with advanced solid tumors harboring the KRAS p.G12C mutation. This study includes dose-escalation and dose-expansion phases to determine safety, tolerability, pharmacokinetics, and preliminary anti-tumor activity[6][8]. 2. A Phase 1b/2 study (NCT06970132) investigating SY-5933 in combination with CT-707 tablets in patients with advanced solid tumors harboring KRAS p.G12C mutation. This study began in June 2025 and is designed to evaluate safety, tolerability, pharmacokinetics, and preliminary efficacy of the combination[1][4]. 3. A study (CTR20251598) examining the effect of food on the pharmacokinetic characteristics of SY-5933 tablets in healthy subjects[1]. ## Administration and Formulation SY-5933 is administered orally in tablet form. In clinical trials, it is being dosed daily in 28-day cycles[3][7]. The specific dosing regimens are being evaluated in the ongoing clinical studies, with some trials exploring a dose of 800 mg once daily in combination therapy[7]. ## Target Patient Population The drug is being developed for patients with: - Advanced KRAS G12C mutated non-small cell lung cancer (NSCLC) - Colorectal cancer with KRAS G12C mutation - Pancreatic cancer with KRAS G12C mutation - Other solid tumors harboring KRAS G12C mutation[1][4][7] SY-5933 represents part of a growing class of targeted therapies specifically designed to address KRAS G12C mutations, which have historically been considered "undruggable" targets. The development of this drug may provide new treatment options for patients with cancers driven by this specific genetic alteration.