Positive Phase III CABINET Results

These results were presented during Poster Session B: Cancers of the Pancreas, Small Bowel, and Hepatobiliary Tract, at 11:30 a.m. PT on January 24 at the American Society of Clinical Oncology 2025 Gastrointestinal Cancers Symposium (ASCO GI 2025).

“Treating neuroendocrine tumors after disease progression can be challenging, including for those with tumors in the gastrointestinal tract, as treatment options are limited,” said Jonathan Strosberg, M.D., President Emeritus, North American Neuroendocrine Tumor Society and Chair, GI Research Program, Moffitt Cancer Center and Research Institute. “This subgroup analysis from the CABINET study showed that cabozantinib improved progression-free survival for patients with tumors arising in the GI tract and provides a more detailed picture of how patients with the most common form of this cancer may benefit from this treatment. As a physician, I’m encouraged by these findings, as they suggest cabozantinib has potential to become a standard of care for patients greatly in need of new options.”

This subgroup analysis included 116 of the 203 patients in the epNET cohort. The most common primary tumor locations were ileum/cecum (54%), small intestine with location not specified (20%), non-cecum colon or rectum (11%), stomach (4%), duodenum (3%), jejunum (3%) and non-specified midgut site (3%).

Cabozantinib was associated with improved PFS by blinded independent central review compared with placebo for patients with GI NET (hazard ratio: 0.50; 95% confidence interval: 0.28-0.88; one-sided stratified log-rank P=0.007). Median PFS was 8.5 months with cabozantinib compared with 5.6 months with placebo. Cabozantinib demonstrated potential benefit across clinical factors, including grade, functional status, concurrent somatostatin agent use, and prior therapy with Lu-177 dotatate or everolimus. One patient achieved a partial response with cabozantinib versus none with placebo, and 48 versus 30 patients, respectively, achieved stable disease.

“These new data add to the robust results from the CABINET trial that demonstrate the benefits of cabozantinib across a wide range of patients with neuroendocrine tumors and further underscore the potential of cabozantinib to become a much-needed new option for those with GI NET, which accounts for the majority of real-world patients with this tumor type,” said Amy Peterson, M.D., Executive Vice President, Product Development & Medical Affairs, and Chief Medical Officer, Exelixis. “We look forward to continuing to work with the U.S. FDA as they review our regulatory application for cabozantinib for the treatment of patients with previously treated advanced neuroendocrine tumors.”

The safety profile of cabozantinib observed in patients with GI NET was consistent with its known safety profile; no new safety signals were identified. The most frequent grade 3/4 adverse events included hypertension (19% of patients receiving cabozantinib and 4% receiving placebo), diarrhea (13% and 4%, respectively) and fatigue (10% and 4%). Three grade 5 events occurred in the cabozantinib arm possibly related to cabozantinib: one due to cardiac arrest and two not specified.

As announced in August 2023, the Alliance for Clinical Trials in Oncology independent Data and Safety Monitoring Board unanimously recommended that the CABINET trial be stopped early and unblinded due to the substantial improvement in PFS observed at an interim analysis. Final PFS results were presented at the 2024 European Society of Medical Oncology Congress and published concurrently in the New England Journal of Medicine. In August 2024, Exelixis announced that the FDA  had accepted the supplemental New Drug Application (sNDA) for cabozantinib for the treatment of previously treated, advanced NET and assigned a Prescription Drug User Fee Act target action date of April 3, 2025.

About CABINET (Alliance A021602); CABINET (Randomized, Double-Blinded Phase III Study of CABozantinib versus Placebo In Patients with Advanced NEuroendocrine Tumors After Progression on Prior Therapy) is sponsored by the National Cancer Institute (NCI), part of the National Institutes of Health, and is being led and conducted by the NCI-funded Alliance for Clinical Trials in Oncology with participation from the NCI-funded National Clinical Trials Network as part of Exelixis’ collaboration through a Cooperative Research and Development Agreement with the NCI’s Cancer Therapy Evaluation Program.

CABINET is a multicenter, randomized, double-blinded, placebo-controlled phase III pivotal trial that had enrolled a total of 298 patients in the U.S at the time of the final analysis. Patients were randomized 2:1 to cabozantinib (60 mg) or placebo in two separately powered cohorts (pancreatic NET, n=95; epNET, n=203). The epNET cohort included patients with the following primary tumor sites: GI tract, lung, unknown primary sites, and other organs. Each cohort was randomized separately and had its own statistical analysis plan. Patients must have had measurable disease per RECIST 1.1 criteria and must have experienced disease progression or intolerance after at least one U.S. FDA-approved line of prior systemic therapy other than somatostatin analogs. The primary endpoint in each cohort was PFS per RECIST 1.1 by blinded independent central review. Secondary endpoints included overall survival, objective response rate and safety. More information about this trial is available at ClinicalTrials.gov.

Citation: Phase III Trial of Cabozantinib to Treat Advanced Neuroendocrine Tumors J.A. Chan and Others10.1056/NEJMoa2403991