Exelixis announces results from expansion cohort of STELLAR-002 trial

Exelixis (EXEL) announced results from an expansion cohort of the phase 1b/2 STELLAR-002 trial evaluating zanzalintinib in combination with either nivolumab or a fixed-dose combination of nivolumab and relatlimab in patients with previously untreated advanced clear cell renal cell carcinoma. These findings, as well as data from multiple dose-escalation cohorts from STELLAR-002, will be presented at the 2025 American Society of Clinical Oncology annual meeting. This expansion cohort of STELLAR-002 included patients with advanced clear cell RCC who received zanzalintinib in combination with either nivolumab or fixed-dose nivolumab and relatlimab in two non-randomized treatment arms. Patients had unresectable advanced or metastatic disease for which they received no prior systemic therapy. Intermediate- or poor-risk disease, per the International Metastatic RCC Database Consortium, accounted for 75% of patients receiving zanzalintinib in combination with nivolumab and 70% of patients receiving zanzalintinib in combination with fixed-dose nivolumab and relatlimab. At a median follow-up of 20.1 months for those receiving zanzalintinib in combination with nivolumab and 15.9 months for those receiving zanzalintinib in combination with fixed-dose nivolumab and relatlimab, the objective response rates were 63% and 40%, respectively. Disease control rates were 90% for both arms. The 12-month duration of response was 73.4% and 74.1%, respectively. Median progression-free survival was 18.5 months and 13.months, respectively. Treatment-emergent adverse events of any grade were reported in all patients. Grade 3/4 TEAEs occurring in at least four patients receiving zanzalintinib in combination with nivolumab included hypertension, diarrhea, aspartate aminotransferase increase, alanine aminotransferase increase and palmar-plantar erythrodysesthesia. Grade 3/4 TEAEs occurring in at least four patients receiving zanzalintinib in combination with fixed-dose nivolumab and relatlimab included hypertension, rash, lipase increase and pulmonary embolism. There were two grade 5 TEAEs in each arm; none were considered related to study treatment. Three patients in the zanzalintinib in combination with nivolumab arm and eight patients in the zanzalintinib in combination with fixed-dose nivolumab and relatlimab arm discontinued all study drugs for treatment-related AEs as assessed by investigator. This analysis of STELLAR-002 included multiple cohorts of patients with advanced solid tumors who received zanzalintinib 100 mg in combination with nivolumab; zanzalintinib 60 mg in combination with fixed-dose nivolumab and relatlimab; or zanzalintinib 100 mg in combination with fixed-dose nivolumab and relatlimab. The most common cancer types for those receiving zanzalintinib in combination with nivolumab were colorectal and prostate cancers, followed by lung cancer and RCC. The most common tumor types in the zanzalintinib in combination with fixed-dose nivolumab and relatlimab cohorts were RCC, followed by prostate cancer, melanoma and colorectal cancer. The findings showed that the toxicity profile of these combinations was manageable and consistent with each monotherapy agent. Preliminary safety, efficacy and pharmacokinetic results supported selection of the 100 mg dose for zanzalintinib for the ongoing expansion cohorts.