Exelixis announces final results from CABINET study

Exelixis announced updated and final data from CABINET, a phase 3 pivotal trial evaluating cabozantinib versus placebo in two cohorts of patients with previously treated neuroendocrine tumors: one cohort with advanced pancreatic neuroendocrine tumors, or pNET, and one cohort with advanced extra-pancreatic NET, or epNET. These data are being presented today at the 2024 European Society for Medical Oncology Congress during the Proffered Paper Session: NETs and Endocrine Tumours at 2:45 p.m. CET and were simultaneously published in the New England Journal of Medicine, or NEJM. The final results from the CABINET study presented today at ESMO and published in NEJM demonstrate continued improvement with cabozantinib in the primary endpoint of progression-free survival, or PFS, by blinded independent central review through the data cutoff of August 24, 2023. In the pNET cohort, at a median follow-up of 13.8 months, the hazard ratio was 0.23; median PFS was 13.8 months for cabozantinib versus 4.4 months for placebo. In the epNET cohort, at a median follow-up of 10.2 months, the HR was 0.38; median PFS was 8.4 months versus 3.9 months, respectively. Upon disease progression, patients were unblinded, and those receiving placebo were permitted to cross over to open-label therapy with cabozantinib. Additional analyses suggest benefits with cabozantinib across all clinical subgroups examined, including primary tumor site, grade and prior systemic anticancer therapy. In the pNET cohort, the objective response rate, or ORR, by BICR was 19% with cabozantinib compared with 0% with placebo. In the epNET cohort, the ORR by BICR was 5% with cabozantinib compared with 0% with placebo. Similar interim overall survival, or OS, results for cabozantinib compared to placebo were observed in both cohorts; HRs for OS were 0.95 for the pNET cohort and 0.86 for the epNET cohort. The safety profile of cabozantinib observed in each cohort was consistent with its known safety profile; no new safety signals were identified. A majority of patients treated with cabozantinib required dose modifications or reductions to manage adverse events. These results were the basis for Exelixis’ supplemental new drug application, or sNDA, for cabozantinib for the treatment of adults with advanced NET. The FDA accepted the sNDA in August and assigned a Prescription Drug User Fee Act target action date of April 3, 2025. In August of 2023, CABINET was stopped and unblinded early due to a dramatic improvement in PFS observed at an interim analysis in both of the trial’s cohorts, per a unanimous recommendation of the Alliance for Clinical Trials in Oncology independent Data and Safety Monitoring Board; all patients were unblinded, and those on placebo were given the option to cross over to active treatment with cabozantinib. Cabozantinib demonstrated a statistically significant and clinically meaningful improvement in PFS versus placebo based on results of both local review and available BICR. Initial results by investigator were presented at ESMO 2023.