ABBISKO-B(02256): The clinical trial application for the oral small molecule pan-KRAS inhibitor ABSK211 has been approved by the NMPA.

ABBISKO-B (02256) announced that the National Medical Products Administration of China (NMPA) has approved the Investigational New Drug (IND) application for ABSK211. ABSK211 is an oral, potent small-molecule pan-KRAS inhibitor that shows broad-spectrum activity against various KRAS genetic alterations and is intended for the treatment of patients with advanced solid tumors harboring KRAS mutations. Previously, ABSK211 received IND approval from the U.S. Food and Drug Administration (FDA) on July 8. Obtaining IND approvals in both China and the U.S. is a key milestone in the global clinical development program for ABSK211. He Yu Medicine will soon initiate an open-label Phase I clinical study aimed at evaluating the safety, tolerability, efficacy, and pharmacokinetic characteristics of ABSK211 in patients with advanced solid tumors carrying KRAS genetic alterations. KRAS is one of the most common oncogenic driver genes in human cancers, with frequent alterations occurring in various solid tumors, including approximately 90% of pancreatic cancers, 35% of colorectal cancers, and 25% of lung cancers. Due to the complex and diverse subtypes of KRAS mutations, it has long been considered one of the most challenging targets in cancer therapy. Although pan-KRAS inhibitors have entered the clinical development phase, there remains an urgent need to further enhance antitumor efficacy. Preclinical studies have shown that ABSK211, as a novel oral pan-KRAS inhibitor, exhibits broad-spectrum and potent inhibitory activity against multiple KRAS mutations such as KRAS G12D, G12C, G12S, G12V, G13D, and KRAS wild-type amplification. In vitro studies indicate that ABSK211 can significantly inhibit the proliferation of various KRAS mutant tumor cell lines in the nanomolar to sub-nanomolar concentration range, while showing almost no activity against KRAS wild-type cell lines with normal copy numbers. In vivo studies further demonstrate that ABSK211 can induce profound and durable tumor regression in multiple KRAS alteration tumor models and possesses potent target binding capabilities. In addition, ABSK211 has exhibited good potential for combination therapy across various tumor models. Research findings indicate that when combined with PRMT5 inhibitors, cetuximab, immunotherapy, and chemotherapy regimens, ABSK211 enhances the antitumor efficacy compared to monotherapy and prolongs the duration of effect, providing support for future exploration of combination treatment strategies.