Dr Ayanambakkam on the Design of the FIT-001 Trial in Renal Cell Carcinoma

“Importantly, with the higher doses of darlifarnib at 5 mg and 8 mg, and with the full dose of cabozantinib at 60 mg, we restricted [trial enrollment] to a cabozantinib-naive population. We had a good mix of both cabozantinib-naive and cabozantinib-exposed patients.”

Adanma Ayanambakkam, MD, MS, the associate program director of Hematology Oncology Fellowship and the director of Infusion Services at the Stephenson Cancer Center at the University of Oklahoma Health Sciences Center, discussed the design of the phase 1a FIT-001 trial (NCT06026410) of darlifarnib (KO-2806) plus cabozantinib (Cabometyx) in renal cell carcinoma (RCC).

FIT-001 evaluated the safety and dosing of darlifarnib in combination with cabozantinib in patients with RCC, Ayanambakkam began. The dose-escalation study initially investigated a lower dose of cabozantinib at 40 mg combined with darlifarnib at 3 mg, 5 mg, or 8 mg, he noted. The trial initially included both patients who had previously received cabozantinib and those who were cabozantinib-naive, he said.

As the study progressed, investigators expanded the evaluation to include the full 60-mg dose of cabozantinib in combination with darlifarnib at the same 3-, 5-, and 8-mg dose levels, Ayanambakkam explained. Importantly, at the higher darlifarnib doses of 5 mg and 8 mg combined with full-dose cabozantinib, enrollment was restricted to patients who had not previously received cabozantinib, he said. This approach allowed investigators to evaluate the combination in both cabozantinib-naive and cabozantinib-exposed populations and account for the different treatment histories of these groups, he said.

Overall, FIT-001 enrolled 72 patients. The median number of prior treatment lines was 2 (range, 1-7), indicating that the study included a substantially pretreated population, Ayanambakkam said. Sixty-seven percent of patients had previously received an immune checkpoint inhibitor combined with a TKI, whereas 38% of patients had previously been treated with cabozantinib, he noted.

The investigators initially focused their data presentation on patients who had already been exposed to cabozantinib, Ayanambakkam noted. More recent data presented at the 2026 Kidney Cancer Research Summit shifted the focus toward the cabozantinib-naive population, providing additional insight into how the combination performs in patients who have not previously received the TKI, he concluded.