FDA Grants Designations for D3S-001 in KRAS G12C-Mutated Cancers

The FDA has granted D3S-001 breakthrough therapy for KRAS G12C some with lung cancer and orphan drug status for KRAS G12C colorectal cancer in adults.

The U.S. Food and Drug Administration (FDA) has granted breakthrough therapy designation to D3S-001 for adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) who have received prior platinum-based chemotherapy and anti-PD-(L)1 immunotherapy but have not been previously treated with a KRAS G12C inhibitor.

The FDA also awarded orphan drug designation to D3S-001 for the treatment of adult patients with KRAS G12C-mutated colorectal cancer (CRC), according to a company news release from D3 Bio, Inc.

Breakthrough therapy designation is intended to accelerate the development and review of therapies that may offer substantial improvements over existing treatments for serious or life-threatening conditions, the news release explained. Orphan drug designation is granted to therapies targeting rare diseases, providing incentives to support clinical development. KRAS mutations are among the most common oncogenic drivers in human cancers, occurring in approximately 25% to 30% of all tumors, the release added.

Specifically, KRAS G12C mutations are found in roughly 12% of NSCLC cases and 3% to 4% of CRC. Patients with KRAS G12C-mutated cancers often experience aggressive disease and limited responses to standard therapies such as chemotherapy and immunotherapy.

“We are very pleased to receive both Breakthrough Therapy and Orphan Drug Designations from the FDA for D3S-001, which highlights its potential to address critical unmet needs in patients with KRAS G12C-mutated cancers,” said George Chen, founder and CEO of D3 Bio, in the news release. “These designations also recognize D3S-001’s novel profile as a next-generation KRAS G12C inhibitor. We look forward to bringing this therapy to patients with support from health authorities.”

Clinical Trial Data Shows Potential for D3S-001 in KRAS G12C Cancers

The regulatory designations are based on data from an ongoing phase 1/2 clinical trial evaluating D3S-001 in patients with advanced solid tumors harboring KRAS G12C mutations. According to the release, the trial has demonstrated durable and compelling responses as measured by RECIST (Response Evaluation Criteria in Solid Tumors), with a favorable safety and tolerability profile.

D3S-001 is designed to potently, selectively and covalently bind the inactive “off” form of the KRAS G12C mutant protein, effectively disrupting its nucleotide cycling between active and inactive states. Preclinical studies show that D3S-001 achieves rapid and complete target engagement at clinically relevant doses, with penetration into the central nervous system. The drug is being evaluated both as a monotherapy and in combination regimens in the ongoing Phase II global trial across multiple tumor types, including NSCLC, CRC and other KRAS G12C-positive cancers.

Why KRAS G12C-Targeted Therapies Matter for Patients

KRAS G12C-targeted therapies represent an important advancement for patients with limited treatment options. Current standard treatments, including chemotherapy and immunotherapy, often fail to achieve durable responses in this population. D3S-001’s next-generation mechanism of action aims to improve outcomes for patients whose cancers harbor this specific mutation, offering potential for more effective and lasting disease control.

“Patients with KRAS G12C-mutated cancers face an aggressive disease course, and treatment options are limited once standard therapies fail,” Chen added. “Our goal with D3S-001 is to provide a therapy that can meaningfully change the trajectory of these cancers and improve patient outcomes.”

The company has published results from preclinical and early clinical studies in journals, including Cancer Discovery and Nature Medicine, demonstrating D3S-001’s robust anti-tumor activity and rapid engagement of KRAS G12C. Further clinical investigation is ongoing, with the aim of confirming these promising early findings and expanding access to patients in need.

Reference

“D3 Bio, Inc. Announces FDA Breakthrough Therapy Designation and Orphan Drug Designation for D3S-001 for the Treatment of Patients with KRAS G12C-Mutated Cancers,” by D3 Bio, Inc. News release, Aug. 28, 2025.

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