Exelixis announces initiation of STELLAR-304 Phase 3 trial of zanzalintinib

Yesterday, Exelixis (EXEL) announced the initiation of STELLAR-304, a phase 3 pivotal trial evaluating zanzalintinib in combination with nivolumab versus sunitinib in patients with advanced non-clear cell renal cell carcinoma, or nccRCC. Zanzalintinib, which was adopted as the generic name for XL092, is a next-generation tyrosine kinase inhibitor in development for multiple advanced tumor types. STELLAR-304 is sponsored by Exelixis and Bristol Myers Squibb (BMY) is providing nivolumab for the trial. STELLAR-304 is a global, multicenter, randomized phase 3 open-label study that will enroll approximately 291 patients with unresectable, locally advanced or metastatic nccRCC with no prior systemic anticancer therapy. One prior systemic adjuvant therapy, including immune checkpoint inhibitor therapy and excluding sunitinib, is allowed for completely resected RCC and if recurrence occurred at least six months after the last dose of adjuvant therapy. Patients will be randomized 2:1 to receive either zanzalintinib in combination with nivolumab or sunitinib monotherapy. The primary objective of the study is to evaluate the efficacy of the combination, as measured by duration of progression-free survival and objective response rate per Response Evaluation Criteria in Solid Tumors version 1.1 as assessed by the Blinded Independent Radiology Committee. The secondary endpoint is duration of overall survival. "In September at ESMO 2022, we presented zanzalintinib phase 1 data which demonstrated promising clinical activity across a range of tumors with a manageable safety profile. We were particularly encouraged by the activity of zanzalintinib in advanced kidney cancer patients, including patients with non-clear cell subtypes. Based on this zanzalintinib data and given that nivolumab has shown activity in non-clear cell kidney cancer, we are excited to evaluate this combination regimen in this population in STELLAR-304. STELLAR-304 is the first and only randomized controlled phase 3 study to focus specifically across non-clear cell renal cell carcinoma subtypes, a patient population with limited clinical data and poorer treatment outcomes. We look forward to continuing our legacy of working towards improving care for all kidney cancer patients," said Vicki L. Goodman, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis.