Darifarnib+Cabo Data in Cabo-naive RCC Patients Supports Combo Benefits; Ph1b Data in 2H27 a Key De-Risking Event

Research evidence excerpt

Darifarnib+Cabo Data in Cabo-naive RCC Patients Supports Combo Benefits; Ph1b Data in 2H27 a Key De-Risking Event

observed efficacy and safety trends in cabo-naive ccRCC patient and the ongoing

randomized Ph1b trial will be important to determine the incremental contribution of

darli beyond cabo monotherapy.

Darli+cabo in 3L+ provides the clearest path to market; Darli+TKI+HIF-2α could

be interesting in 2L setting

Mgmt characterized 3L+ RCC as the clearest initial path to market for

darlifarnib+cabozantinib. Mgmt emphasized that the strategic value of

darlifarnib extends beyond the current cabo combination and highlighted its

potential to enhance activity across multiple TKI backbones and potentially other

targeted therapies. Mgmt compared the cabo-naïve FIT-001 results (ORR 33%-

50%; pooled mPFS 13 months) with both current 3L benchmarks (tivozanib ORR

18%, mPFS 5.6 months; belzutifan ORR 23%, mPFS 5.6 months) and reported 2L

cabozantinib benchmarks (ORR 27.5%-40%; mPFS 8.3-10.7 months), suggesting

the dataset could support development opportunities in both settings.

Investigators noted that increasing use of belzutifan earlier in the treatment

paradigm may create a growing population of HIF-2α-exposed patients,

reinforcing the need for differentiated mechanisms in later-line RCC.

Mgmt sees potential for Darli+TKI+HIF-2α triplets as 2L strategy. While

mgmt continues to view 2L RCC as a potentially larger commercial opportunity, it

has not finalized a registrational strategy and repeatedly highlighted the ongoing

platform effort as a mechanism to identify the most suitable combination partner

and treatment setting. Although mgmt acknowledged that emerging HIF-2α

regimens are raising the efficacy benchmark in 2L RCC, both mgmt and