Adanma Ayanambakkam, MD, on darlifarnib/cabozantinib activity in ccRCC

In the following video, Adanma Ayanambakkam, MD, MS, highlights efficacy data from the phase 1 FIT-001 trial (NCT06026410), exploring the combination of darlifarnib and cabozantinib (Cabometyx) in patients with previously treated clear cell renal cell carcinoma (ccRCC). These data were presented at the 2026 International Kidney Cancer Symposium (IKCS): Europe in Paris, France.¹

Ayanambakkam is a medical oncologist at the Stephenson Cancer Center of the University of Oklahoma Health Sciences Center in Oklahoma City, Oklahoma.

Early efficacy data from FIT-001 highlight encouraging antitumor activity despite the heavily pretreated population. Among 16 response-evaluable patients with prior cabozantinib exposure, the objective response rate (ORR) was approximately 44%. Notably, the disease control rate (DCR) reached 94%, with 15 of 16 patients achieving a response of partial response or stable disease. Tumor shrinkage among responders ranged from 32% to 47%. Although the median duration of response has not yet been reached, treatment durations have ranged from 8 weeks to as long as 56 weeks and ongoing, with the longest response extending beyond 11 months.

Ayanambakkam emphasized that these findings are particularly notable given that patients had previously progressed on cabozantinib, suggesting that the addition of darlifarnib may help overcome resistance mechanisms. He pointed to the role of mTORC1 signaling in adaptive resistance to VEGFR tyrosine kinase inhibitors, including cabozantinib, and highlighted how darlifarnib—a selective farnesyl transferase inhibitor—targets this pathway. By inhibiting mTORC1 without affecting mTORC2, the agent may offer a more precise and potentially better-tolerated strategy compared with earlier mTOR-directed therapies such as everolimus-based combinations.

Importantly, the clinical activity observed in FIT-001 appears to mirror preclinical findings, where darlifarnib demonstrated the ability to resensitize treatment-resistant tumor models and produce deep, durable responses in combination therapy.² The consistency between laboratory and early clinical results reinforces the biologic rationale for this approach and suggests that the combination could address a key unmet need in the post-cabozantinib setting. With a manageable safety profile and promising durability signals, these preliminary data support continued investigation of darlifarnib plus cabozantinib as a potential therapeutic strategy for patients with advanced ccRCC.

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