Dr Ayanambakkam on the Safety Profile of Darlifarnib Plus Cabozantinib in ccRCC

“The safety and tolerability profile has been promising. The darlifarnib/cabozantinib combination has exhibited a manageable safety profile across all dose levels in the RCC group.”

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 safety data with darlifarnib (KO-2806) in combination with cabozantinib (Cabometyx) in patients with clear cell renal cell carcinoma (RCC).

Findings from the phase 1a/1b FIT-001 trial (NCT06026410) presented during the 2026 International Kidney Cancer Symposium: Europe showed that patients with RCC who received the combination across dose-levels (n = 70) experienced dose-limiting toxicities at a rate of 6%, Ayanambakkam said. The most common any-grade treatment-emergent adverse effects (TEAEs) included neutropenia (41%), fatigue (30%), diarrhea (26%), nausea (26%), and thrombocytopenia (21%). The most common grade 3 or higher TEAE related to darlifarnib was neutropenia, which occurred at a rate of 30%, he added.

Darlifarnib discontinuation (6%) or dose reductions (13%) were infrequent, Ayanambakkam noted. Cabozantinib dose reductions (26%) and interruptions (71%) were also reported, he added.

Serious adverse effects (SAEs) related to darlifarnib (9%), any-grade cabozantinib-related TEAEs (93%), grade 3 or higher cabozantinib-related TEAEs (46%), and SAEs related to cabozantinib (13%) were all reported. Any-grade TEAEs occurred at a rate of 83%; grade 3 or higher TEAEs were reported at a rate of 50%.

Overall, the data indicate that the safety and tolerability profile of darlifarnib plus cabozantinib is promising, Ayanambakkam said. The combination exhibited a manageable safety profile across all dose levels, he concluded.

Disclosures: Ayanambakkam reported consulting or advisory roles with AVEO, Pfizer/Astellas, Johnson & Johnson, and Kura Oncology. He received travel, accommodations, and/or expenses from Kura Oncology and research funding from Regeneron.