Kura Oncology reports Phase 1a FIT-001 data showing up to 50% response rates and 13-month median PFS with darlifarnib plus cabozantinib in cabozantinib-naïve advanced clear cell renal cell carcinoma.
Written By: Nalam Karthik, PharmD
Reviewed By: Pharmacally Editorial Team
Kura Oncology has reported updated Phase 1a data from the ongoing FIT-001 trial (NCT06026410), showing durable clinical activity and a manageable safety profile for darlifarnib in combination with cabozantinib in patients with locally advanced or metastatic clear cell renal cell carcinoma (ccRCC). The results, presented at the 2026 Kidney Cancer Research Summit (KCRS), strengthen the rationale for advancing the regimen into randomized testing in patients who have not previously received cabozantinib.
The combination produced encouraging antitumor activity in a difficult-to-treat population that had received prior systemic therapy but remained cabozantinib-naïve. Investigators also reported prolonged disease control, with several patients continuing treatment at the time of data cutoff.
Scientific and Clinical Context
Clear cell renal cell carcinoma is the most common subtype of kidney cancer and frequently develops resistance to available therapies after treatment with immune checkpoint inhibitors and vascular endothelial growth factor receptor (VEGFR)-targeted agents. Patients progressing after frontline immunotherapy continue to face limited therapeutic options.
Darlifarnib is a next-generation farnesyl transferase inhibitor that selectively blocks farnesylation of RHEB, resulting in inhibition of mTORC1 while sparing mTORC2. This selective mechanism may enhance the activity of VEGFR-targeted therapies such as cabozantinib by providing complementary inhibition of tumor growth pathways.
Phase 1a Trial Demonstrates Durable Responses
The ongoing FIT-001 study is evaluating darlifarnib plus cabozantinib in patients with advanced ccRCC. Among 34 cabozantinib-naïve patients included in the efficacy analysis, objective response rates ranged from 33% to 50% across the evaluated darlifarnib dose levels.
Across pooled dose cohorts, the combination achieved a median progression-free survival of 13 months. Median duration of response was not yet estimable for most dose levels because several responses remained ongoing. More than half of treated patients continued receiving therapy at the data cutoff, supporting durable clinical benefit.
Investigators noted that the observed efficacy compares favorably with historical outcomes reported for tyrosine kinase inhibitor and HIF-2α inhibitor monotherapies in similar treatment settings, although cross-trial comparisons should be interpreted cautiously.
Safety Profile Supports Continued Development
Safety findings included 72 patients treated across dose levels. The combination demonstrated a manageable tolerability profile consistent with the known safety profiles of darlifarnib and cabozantinib individually.
During the dose-limiting toxicity assessment period, supportive care for neutropenia was not permitted. Neutropenia was successfully managed with dose interruptions, dose reductions, and supportive care once allowed after the initial evaluation period. Investigators reported that the combination remained tolerable even when administered with full-dose cabozantinib.
Clinical Implications
Adanma Ayanambakkam, M.D., M.S., Assistant Professor of Hematology Oncology and Assistant Medical Director of the Clinical Trials Office at the Stephenson Cancer Center, University of Oklahoma Health Sciences Center, said the response rates and progression-free survival observed with the combination are encouraging in this refractory, previously treated population, where treatment options remain limited after immunotherapy and prior VEGFR-targeted therapy. She added that continued follow-up will further define the durability of benefit.
Mollie Leoni, M.D., Chief Medical Officer of Kura Oncology, said the updated Phase 1a findings support the potential for darlifarnib to enhance VEGFR-targeted therapy and have guided dose selection for the randomized Phase 1b portion of FIT-001. She noted that cabozantinib-naïve patients represent an increasingly important treatment population as cabozantinib is often reserved for later lines of therapy following immunotherapy-based regimens.
Path Forward
Kura Oncology is currently enrolling patients across the United States and Europe into the randomized Phase 1b portion of FIT-001. The study compares darlifarnib plus cabozantinib with cabozantinib alone in cabozantinib-naïve patients with refractory clear cell renal cell carcinoma.
The randomized trial will identify the recommended Phase 3 dose while generating comparative efficacy and safety data to support a planned registrational study targeted for 2028. Longer-term follow-up from Phase 1a and data from Phase 1b will further clarify whether the combination can improve outcomes in the second- and third-line treatment of advanced renal cell carcinoma.
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About the Writer
Nalam Karthik (LinkedIn) is a healthcare writer and PharmD graduate with interests in pharmacovigilance, drug safety, clinical data analysis, and quality assurance. He is passionate about translating clinical and pharmaceutical knowledge into accessible healthcare content while staying engaged with advancements in drug development and patient safety initiatives.