STELLAR-001: Single-Agent Zanzalintinib for Previously Treated Advanced RCC

Zanzalintinib—a novel, multitargeted tyrosine kinase inhibitor that targets VEGFR, MET, and TAM kinases—shows promising preliminary antitumor activity and manageable toxicity in patients with previously treated advanced clear cell renal cell carcinoma (ccRCC), according to results of the STELLAR-001 study presented at the 2023 International Kidney Cancer Symposium: North America.

Merit Award winner and lead author Sumanta Pal, MD, FASCO, of the City of Hope, presented the initial results of single-agent zanzalintinib in a ccRCC expansion cohort, including outcomes for patients with previous exposure to cabozantinib.

A total of 32 patients with advanced ccRCC and an Eastern Cooperative Oncology Group (ECOG) performance status of ≤1 and radiographic progression on at least 1 prior systemic therapy for inoperable locally advanced or metastatic disease were enrolled in the expansion cohort. Patients received zanzalintinib at a starting dose of 100 mg once daily. Objective response rate (ORR) by investigator per Response Evaluation Criteria in Solid Tumors 1.1 and safety were assessed.

The median age of the patient sample was 64 years and 72% were male, Dr. Pal noted. Eighty-one percent had International Metastatic Renal Cell Carcinoma Database Consortium intermediate-risk disease, while 6% had poor-risk disease. Patients had received a median of 2 lines of prior therapy, and 53% (n=17) of patients had received prior cabozantinib.

In the cabozantinib and cabozantinib-naïve subgroups, 59% and 36% of patients, respectively, had an ECOG performance status of 1, and 59% and 14% of patients, respectively, had at least 3 prior lines of therapy.

The median follow-up was 7 months. At data cutoff, 56% (n=18) of patients remained on zanzalintinib treatment. The ORR was 31%, and the disease control rate (DCR) was 88%. In the cabozantinib and cabozantinib-naïve subgroups, the ORR was 43% and 24%, respectively, and the DCR was 86% and 94%, respectively.

“Single-agent zanzalintinib showed promising preliminary antitumor activity and manageable toxicity in patients with previously treated advanced ccRCC,” Dr. Pal and colleagues concluded. “Antitumor activity was observed in both cabozantinib-naïve and cabozantinib-exposed patient populations, with most patients in both subgroups achieving disease control.”