Dr Pal on Outcomes With the Use of Zanzalintinib in Relapsed/Refractory ccRCC

Sumanta Kumar Pal, MD, FASCO, chair, Kidney and Bladder Cancer Disease Team, co-director, Kidney Cancer Program, professor, Department of Medical Oncology and Therapeutics Research, City of Hope, discusses outcomes with the use of zanzalintinib (XL092) in patients with relapsed/refractory clear cell renal cell carcinoma (ccRCC).

At the 2023 International Kidney Cancer Symposium, Pal shared results from the expansion cohort of the phase 1b STELLAR-001 trial (NCT03845166) assessing the next-generation TKI, zanzalintinib, in patients with previously treated ccRCC and other locally advanced or metastatic solid tumors. Findings demonstrated that at a median follow-up of 8.3 months, patients with ccRCC (n = 32) achieved an objective response rate (ORR) of 38% and a disease control rate (DCR) of 88%. Notably, anti-tumor activity was observed in patients who had progressed on a prior VEGF TKI, including cabozantinib (Cabometyx), with evaluable patients (n = 26) experiencing an ORR and DCR of 35% and 92%, respectively. Notably, 81% of all patients had intermediate-risk disease. The safety profile was consistent across cohorts, with manageable adverse effects (AEs).

In this trial, patients were administered zanzalintinib orally at a daily dose of 100 mg until disease progression or the development of intolerable toxicities, Pal begins. The study yielded an impressive ORR and, notably, when examining patients without prior exposure to cabozantinib (n = 14), the ORR was 57%.

Pal details that the results from the ccRCC cohort are notable for 2 key reasons. Firstly, the ORR exceeded typical expectations for a refractory disease study, Pal explains. Secondly, an ORR approaching 60% is unprecedented, especially among patients with previous cabozantinib exposure, he states.

Looking to safety, the agent had a favorable toxicity profile similar to other TKIs, particularly in terms of limited incidences of stomatitis and hand-foot syndrome, Pal continues, saying that these are toxicities that pose significant challenges. Pal concludes by saying that these findings align with his personal clinical experience, where patients who struggled with standard agents have shown positive outcomes with zanzalintinib, providing a source of encouragement.