Kura Oncology’s darlifarnib plus adagrasib shows early activity in KRAS G12C cancers, with strong responses across PDAC, NSCLC, and CRC.
Written By: Farha Farheen, PharmD
Reviewed By: Pharmacally Editorial Team
Kura Oncology presented encouraging Phase 1 data from the FIT-001 trial (NCT06026410) evaluating darlifarnib (KO-2806), a next-generation farnesyl transferase inhibitor, in combination with adagrasib at the 2026 ASCO Annual Meeting. The regimen demonstrated notable activity across heavily pretreated KRAS G12C-mutated solid tumors, including pancreatic, lung, and colorectal cancers.
Among 26 response-evaluable patients, 77% achieved tumor shrinkage, including 94% of KRAS inhibitor-naïve patients. Objective response rates reached 67% in pancreatic ductal adenocarcinoma (PDAC), 50% in non-small cell lung cancer (NSCLC), and 29% in KRAS inhibitor-naïve colorectal cancer (CRC).
Investigators also reported a confirmed partial response with 84% target lesion reduction in an NSCLC patient previously treated with a KRAS inhibitor, supporting potential activity in resistant disease settings.
Mechanistic Rationale
Darlifarnib targets resistance pathways downstream of KRAS signaling by inhibiting RHEB farnesylation and suppressing mTORC1 activity, a pathway frequently linked to adaptive resistance to targeted therapies. The strategy builds on earlier clinical evidence supporting farnesyl transferase inhibitor combinations with VEGFR and PI3Kα inhibitors and further validates mTORC1-RHEB blockade as a potential resistance-targeting approach.
Safety and Dosing
Patients received darlifarnib at 3 mg, 5 mg, or 8 mg once daily on days 1-7 and 15-21 of each 28-day cycle alongside adagrasib 400 mg twice daily. Kura confirmed that the 8 mg dose will not advance for further evaluation.
Median follow-up ranged from 6.7 months in PDAC to 8.9 months in CRC, while 37% of patients remained on treatment at the March 25, 2026 data cutoff. The combination showed a manageable safety profile, with responses observed across dose levels and tumor types. No unexpected safety signals were reported.
Executive Commentary
Chief Executive Officer Troy Wilson said the findings support Kura’s farnesyl transferase inhibitor platform as a precision combination strategy for overcoming resistance to targeted therapies.
Investigators from The University of Texas MD Anderson Cancer Center highlighted the potential of targeting downstream resistance signaling to deepen and extend KRAS inhibitor responses.
Future Clinical Expansion
Kura plans to continue advancing darlifarnib combination studies across KRAS-driven cancers and additional targeted therapy settings. The company will host a virtual investor event on June 3 to discuss the FIT-001 data and outline future development plans.
Reference
About the Writer
Farha Farheen, PharmD (LinkedIn) is a pharmacy professional with a strong interest in pharmacovigilance and clinical research. She has completed her Doctor of Pharmacy (Pharm.D) along with her internship as a Clinical Pharmacist. She has hands-on experience in adverse drug reaction (ADR) reporting, safety data documentation, and pharmacovigilance workflows, and is proficient in using VigiFlow. She is also a patent holder for an antibacterial formulation enriched with bioactive substances, granted by the German Patent and Trademark Office