Dr Runcie on Treatment Approaches in RCC After Progression on Adjuvant Therapy

"The current challenges are that there's no standard regimen [after progression on adjuvant therapy]. We don't know what the most optimal regimen is. Some patients may receive [cabozantinib], some may receive [lenvatinib], and some may receive lenvatinib plus IO.”

Karie Danielle Keera Runcie, MD, an assistant professor of medicine at Columbia University Herbert Irving Comprehensive Cancer Center and medical oncologist at NewYork-Presbyterian/Columbia University Irving Medical Center, discussed current treatment approaches for patients with clear cell renal cell carcinoma (RCC) who experience disease progression during adjuvant therapy, and highlighted the potential role for the novel TKI zanzalintinib (XL092) in the treatment paradigm.

Runcie explained that there is lack of standardized treatment approaches in advanced RCC following progression on adjuvant therapy, noting that current regimens vary widely. Patients may receive cabozantinib (Cabometyx) alone, lenvatinib (Lenvima) alone, or a combination of a TKI and an immuno-oncology agent, she said. Although adjuvant pembrolizumab (Keytruda) demonstrated a disease-free survival benefit in the phase 3 KEYNOTE-564 trial (NCT03142334), recurrence remains a risk for this patient population.

Runcie emphasized that zanzalintinib , a multi-targeted TKI, demonstrates activity against VEGF signaling as well as potential immunomodulatory properties, which may distinguish it from prior agents. Data from the phase 1b STELLAR 002 trial (NCT05176483) presented at the 2025 ASCO Annual Meeting showed that zanzalintinib plus nivolumab (Opdivo) with or without relatlimab (Opdualag) was generated similar safety data compared with the checkpoint inhibitors alone in patients with advanced solid tumors, including RCC.

The ongoing phase 2 EXACT trial (NCT06863311) is further investigating zanzalintinib in combination with immunotherapy for patients with RCC who experience disease progression during adjuvant anti–PD-1/PD-L1 therapy.

Although additional prospective data are needed to validate early findings for zanzalintinib, Runcie noted that the distinct toxicity profile of the agent may offer an advantage in later-line settings where cumulative toxicity from chronic VEGF inhibition is a concern.