Dr Pal on the Rationale for Investigating 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 the rationale for treating patients with zanzalintinib (XL092) in relapsed/refractory clear cell renal cell carcinoma (ccRCC).

At the 2023 International Kidney Cancer Symposium, Pal shared a read-out of data from the expansion cohort of the phase 1b STELLAR-001 study (NCT03845166). The STELLAR-001 trial encompasses several cohorts, the first being a dose-escalation portion aimed at determining the optimal dosage for zanzalintinib. This was determined to be a dose of 100 mg, he begins. The focus of his presentation centered on one specific cohort of 32 patients with ccRCC. 

Patients in the dose-expansion cohort exhibited aggressive disease characteristics, with more than 30 patients exhibiting bone and liver metastases, respectively, he expands. A significant portion of these patients had been previously exposed to therapy, with over 40% having received 3 prior treatments, Pal states. This establishes a patient population with notably aggressive disease features. Pal says that zanzalintinib holds promise for patients with RCC in various settings. The agent’s median duration of response (DOR) of 7.4 months, as observed in the cabozantinib (Cabometyx)-naive cohort, is noteworthy, he emphasizes. For patients previously exposed to cabozantinib, the median DOR has not been reached at this point. However, the current survival curves reveal ongoing responses with zanzalintinib in many patients. Notably, most patients’ first response occurred around the time of the initial post-baseline assessment, he explains. Regarding toxicity, the incidence of any-grade treatment-related adverse effects (TRAEs) was 97%, while the rate of grade 3 TRAEs was 44%. No grade 4 or 5 treatment-related AEs were observed.

These promising data support the continued investigation of zanzalintinib alongside nivolumab (Opdivo) in the STELLAR-304 clinical trial (NCT05678673), where it is being validated against sunitinib (Sutent), he continues. Several ongoing studies are evaluating otherzanzalintinib combinations, Pal concludes.