Exelixis Releases Final Phase 3 CABINET Study Results on Cabozantinib in Advanced Neuroendocrine Tumors at ESMO 2024

Exelixis, Inc. (Nasdaq: EXEL) has recently announced the final data from the CABINET study, a significant phase 3 trial evaluating the efficacy of cabozantinib (CABOMETYX®) compared to a placebo in patients with previously treated neuroendocrine tumors. The trial focused on two distinct patient groups: those with advanced pancreatic neuroendocrine tumors (pNET) and those with advanced extra-pancreatic neuroendocrine tumors (epNET). The findings were shared at the 2024 European Society for Medical Oncology Congress (ESMO 2024) and published simultaneously in the New England Journal of Medicine (NEJM).

Dr. Jennifer Chan, the study chair and Clinical Director of the Gastrointestinal Cancer Center at Dana-Farber Cancer Institute, highlighted that the CABINET study reflects real-world clinical practice by including a wide range of patients regardless of tumor site, grade, and other factors. She expressed optimism about the outcomes, suggesting that cabozantinib could offer a meaningful treatment benefit for patients with advanced neuroendocrine tumors who have limited options.

The final results showed a marked improvement in progression-free survival (PFS) for cabozantinib. In the pNET cohort of 95 patients, the median follow-up was 13.8 months, with a hazard ratio (HR) of 0.23, indicating a significant reduction in the risk of disease progression or death compared to placebo. The median PFS for cabozantinib was 13.8 months, compared to just 4.4 months for the placebo group. Similarly, in the epNET cohort of 203 patients, the median follow-up was 10.2 months, and the HR was 0.38, with median PFS being 8.4 months for cabozantinib versus 3.9 months for placebo.

Upon the progression of the disease, patients who were initially receiving placebo were allowed to switch to open-label cabozantinib treatment. Additional analyses indicated that cabozantinib provided benefits across all examined clinical subgroups, including different primary tumor sites and previous anticancer therapies. Specifically, the objective response rate (ORR) in the pNET cohort was 19% with cabozantinib compared to 0% with placebo, and in the epNET cohort, it was 5% versus 0%, respectively.

Dr. Amy Peterson, Executive Vice President at Exelixis, noted the severe prognosis faced by patients with advanced neuroendocrine tumors and emphasized that the updated data support cabozantinib's potential to become a new treatment standard by significantly delaying disease progression. She reiterated Exelixis' commitment to working with the FDA to expedite the availability of this treatment for patients with advanced neuroendocrine tumors.

The safety profile of cabozantinib was consistent with previous findings, with no new safety issues identified. Most patients required dose adjustments to manage adverse effects, which were in line with the known safety profile of the drug.

These promising results have been the foundation for Exelixis' supplemental new drug application (sNDA) submitted to the FDA, which was accepted in August, with a target action date set for April 3, 2025. The CABINET trial was prematurely stopped in August 2023 following an interim analysis that showed significant PFS improvements in both trial cohorts. As a result, patients on placebo were given the option to switch to cabozantinib.

The CABINET trial (Alliance A021602) was sponsored by the National Cancer Institute (NCI) and conducted through the NCI-funded Alliance for Clinical Trials in Oncology, involving multiple centers across the U.S. The study enrolled 298 patients who were randomized to receive either cabozantinib or a placebo in a 2:1 ratio.

Neuroendocrine tumors (NETs) are cancers that originate in the neuroendocrine cells of the body, which possess characteristics of both nerve cells and hormone-producing cells. The incidence of NETs has been on the rise, with an estimated 161,000 to 192,000 people in the U.S. currently living with advanced or metastatic forms of the disease. Treatment options for advanced NETs include somatostatin analogs, chemotherapy, targeted therapy, and peptide-receptor radionuclide therapy.