Kura Oncology reported encouraging early Phase 1a data at ASCO 2026 showing darlifarnib plus adagrasib achieved notable responses across KRAS G12C-mutant pancreatic, lung, and colorectal cancers, supporting expansion into a multi-combination platform strategy.
Written By: Chikkula Pavan Kumar, PharmD
Reviewed By: Pharmacally Editorial Team
Kura Oncology presented new clinical and translational data at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, highlighting darlifarnib as a potential combination backbone for KRAS-mutant cancers. Early Phase 1a results from the ongoing FIT-001 study showed encouraging anti-tumor activity when darlifarnib was combined with the KRAS G12C inhibitor adagrasib in heavily pretreated patients with pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), and colorectal cancer (CRC).
Targeting Adaptive Resistance
Darlifarnib is a next-generation farnesyl transferase inhibitor (FTI) that blocks RHEB farnesylation and suppresses mTORC1 signaling, a pathway linked to adaptive resistance following KRAS inhibition. Preclinical data presented at ASCO showed enhanced anti-tumor activity when darlifarnib was combined with multiple classes of RAS-targeted therapies, including mutant-selective KRAS inhibitors, pan-KRAS inhibitors, pan-RAS approaches, and multi-selective RAS(ON) inhibitors.
Researchers also observed tumor regressions in models previously exposed to KRAS inhibitors, supporting a potential role for darlifarnib in overcoming acquired resistance and broadening the effectiveness of targeted therapies.
FIT-001 Trial Results
The ongoing Phase 1a FIT-001 study (NCT06026410) is evaluating darlifarnib plus adagrasib in patients with KRAS G12C-mutated solid tumors. Among 26 response-evaluable patients, tumor shrinkage occurred in 77% overall and in 94% of KRAS inhibitor-naïve patients.
Confirmed objective response rates (ORRs) were:
- 67% in pancreatic ductal adenocarcinoma
- 50% in non-small cell lung cancer
- 29% in KRAS inhibitor-naïve colorectal cancer
Clinical activity was also observed in patients previously treated with KRAS inhibitors, suggesting the combination retains activity beyond initial KRAS-targeted therapy.
Median follow-up ranged from 6.7 to 8.9 months across tumor types, and approximately 37% of patients remained on treatment at data cutoff. The combination showed a manageable safety profile, with responses observed across dose levels. Kura selected lower dose levels for future development and will not advance the 8 mg dose.
While cross-trial comparisons should be interpreted cautiously, response rates compared favorably with historical adagrasib monotherapy results, supporting the potential for deeper and more durable responses.
Expanding a Combination Platform
The ASCO findings represent the third clinical validation of Kura’s FTI-based combination strategy, following previously reported activity in renal cell carcinoma and PIK3CA-mutated head and neck cancer.
Building on these results, Kura plans to launch a flexible platform study evaluating darlifarnib across multiple targeted therapy combinations and disease settings. The first planned combination will pair darlifarnib with daraxonrasib in second-line and later KRAS-mutant pancreatic cancer, with Phase 1a evaluation expected to begin in early 2027.
Clinical Implications
Chief Executive Officer Troy Wilson said the growing clinical and translational evidence supports darlifarnib’s potential as a broader platform for molecularly defined cancers. Chief Medical Officer Mollie Leoni added that the expanding KRAS and RAS inhibitor landscape creates opportunities to combine darlifarnib with multiple next-generation targeted therapies.
Together, the findings support further development of darlifarnib across KRAS-driven cancers and provide the rationale for expanding the program into next-generation RAS-targeted combinations.
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About the Writer
Chikkula Pavan Kumar (LinkedIn), PharmD is a Doctor of Pharmacy with a keen interest in clinical pharmacy, pharmacovigilance, and evidence-based practice. In his words, he is passionate about patient safety and translating complex medical information into clear, research-driven communication.