Dr Ayanambakkam on the Safety of Darlifarnib Plus Cabozantinib in RCC KD

“Overall, [it was] a very convincing, safe toxicity profile with expected AEs from cabozantinib-based TKIs.”

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 safety profile of darlifarnib (KO-2806) plus cabozantinib (Cabometyx) in renal cell carcinoma (RCC) that was reported in the phase 1a FIT-001 trial (NCT06026410).

The safety analysis of the FIT-001 study included both cabozantinib-naive and cabozantinib-exposed patients and showed that adding darlifarnib did not appear to worsen the expected toxicity profile associated with TKI therapy, Ayanambakkam began. In particular, investigators did not observe increased rates of common cabozantinib-related adverse effects (AE) such as diarrhea, stomatitis, or hand-foot syndrome, he noted. This suggests that the combination did not substantially exacerbate the toxicities typically associated with cabozantinib-based treatment, he added.

A notable AE associated with the addition of darlifarnib was neutropenia, Ayanambakkam emphasized. Approximately 65% of patients experienced grade 3 or higher AEs, with about half of these events attributed to darlifarnib monotherapy, he added. Neutropenia represented the predominant toxicity and was considered an on-target AE related to darlifarnib’s mechanism of action, he said. Despite its frequency, investigators reported that neutropenia was manageable, primarily through dose modifications and treatment interruptions, he added.

The incidence of neutropenia was particularly notable during the initial dose-limiting toxicity assessment periods, when prophylactic granulocyte colony-stimulating factor (G-CSF) was not permitted, Ayanambakkam said. As the study progressed and G-CSF prophylaxis was allowed, investigators observed less neutropenia, suggesting that supportive care could help improve management of this treatment-related toxicity, he added.

Overall, the safety findings provided a favorable assessment of the darlifarnib and cabozantinib combination, Ayanambakkam said. The regimen maintained the expected AE profile associated with cabozantinib-based TKIs without evidence of increased diarrhea, stomatitis, or hand-foot syndrome, he concluded.