Adanma Ayanambakkam, MD, discusses phase 1 data on darlifarnib plus cabozantinib in RCC

In the following interview, Adanma Ayanambakkam, MD, MS, discusses the rationale and key findings from the phase 1 FIT-001 trial evaluating the combination of darlifarnib and cabozantinib (Cabometyx) in patients with advanced renal cell carcinoma. These data were presented at the 2026 Kidney Cancer Research Summit in Boston, Massachusetts.

The FIT-001 study was designed to evaluate the safety and preliminary efficacy of darlifarnib in combination with cabozantinib. The dose-escalation trial assessed darlifarnib at 3 mg, 5 mg, and 8 mg alongside cabozantinib 40 mg and 60 mg. Ayanambakkam noted that the 5-mg and 8-mg darlifarnib cohorts paired with cabozantinib 60 mg enrolled only cabozantinib-naive patients, which formed the basis of the data presented at KCRS.

The cabozantinib-naive cohort consisted of a heavily pretreated population, with over 50% of patients having received 2 or more prior lines of therapy. According to Ayanambakkam, the combination demonstrated a manageable and expected safety profile, with adverse events largely consistent with those previously observed with tyrosine kinase inhibitors. The most common treatment-emergent adverse events were diarrhea (64%), fatigue (50%), and neutropenia (47%). Ayanambakkam explained that supportive care, including for neutropenia, was not permitted during the dose-limiting toxicity period.

In addition to its favorable tolerability, the combination produced encouraging antitumor activity in this heavily pretreated population. Objective response rates ranged from approximately 33% to 50%, with the highest response rate observed in the darlifarnib 5 mg plus cabozantinib 60 mg cabozantinib-naive cohort. Disease control rates ranged from 80% to 100%, and responses appeared durable, with a median progression-free survival of approximately 13 months. Ayanambakkam highlighted that 6-month and 9-month progression-free survival rates of 74% and 60%, respectively, underscore the durability of benefit and reflect the ability to effectively manage treatment-related adverse events through dose modifications when needed.

REFERENCE

1. Ayanambakkam A, Zakharia Y, Rosen LS, et al. Farnesyl transferase inhibitor (FTI) darlifarnib combined with cabozantinib in renal cell carcinoma (RCC): Updated phase 1a results from FIT-001. Presented at: 2026 Kidney Cancer Research Summit. July 23-24, 2026. Boston, Massachusetts. Abstract 12