On August 28, 2025 D3 Bio, Inc, a clinical-stage oncology company focuses on discovery and development of precision oncology therapies, reported that the U.S. Food and Drug Administration (FDA) has granted a Breakthrough Therapy Designation to D3S-001, the company’s next generation KRAS G12C-selective inhibitor, for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC who have received prior chemotherapy and immunotherapy but have not been previously treated with a KRAS G12C inhibitor (Press release, D3 Bio, AUG 28, 2025, View Source [SID1234655563]). Additionally, D3S-001 has been granted Orphan Drug Designation for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic CRC.
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The Breakthrough Therapy and Orphan Drug Designations are based on clinical data from an ongoing Phase 1/2 study (NCT05410145) evaluating D3S-001 in patients with advanced solid tumors harboring a KRAS G12C mutation. Results from this ongoing clinical trial demonstrated highly compelling and durable efficacy according to RECIST (Response Evaluation Criteria in Solid Tumors) with a favorable safety and tolerability profile.
"We are very pleased to receive both Breakthrough Therapy and Orphan Drug Designations from the FDA for D3S-001, which highlights D3S-001’s promising potential to address critical unmet needs in patients with KRAS G12C-mutated cancers," said George Chen, Founder and CEO of D3 Bio. "These designations also recognize D3S-001’s novel profile as a next-generation KRAS G12C inhibitor. We look forward to bringing this exciting new treatment to patients with support and collaboration from health authorities."
KRAS mutations are among the most common oncogenic drivers in human cancers, found in approximately 25 to 30% of all tumors. The KRAS G12C mutation occurs in approximately 12% of NSCLC cases and 3 to 4% of CRC. Patients with KRAS G12C-mutated cancers often have more aggressive disease and limited responses to standard therapies, such as immunotherapy and/or chemotherapy.
About D3S-001
D3S-001 is a next-generation KRAS G12C inhibitor designed to achieve rapid and complete KRAS G12C target engagement. D3S-001 potently, selectively, and covalently binds to the oncogenic RAS (Off) form of the RAS G12C variant, functionally abolishing the nucleotide cycling between RAS (Off) and RAS (On) forms of the G12C mutant protein. In preclinical investigations, D3S-001 demonstrated high covalent potency, complete engagement of KRAS G12C at clinically relevant doses and CNS penetration properties. D3S-001 is currently under evaluation as monotherapy and in combination regimens in a Phase II global clinical trial in patients with advanced solid tumors harboring KRAS G12C mutations, including NSCLC, CRC, and other tumor types. Key publications:
D3S-001, a KRAS G12C Inhibitor with Rapid Target Engagement Kinetics, Overcomes Nucleotide Cycling, and Demonstrates Robust Preclinical and Clinical Activities. Cancer Discov. (2024)14 (9):1675–1698.
D3S-001 in advanced solid tumors with KRASG12C mutations: a phase 1 trial. Nat Med. 2025 Aug;31(8):2768-2777.