Cabozantinib Efficacy Prompts CABINET Trial Unblinding in Advanced Pancreatic and Extra-Pancreatic NETs

Interim data from the phase 3 CABINET trial (NCT03375320) demonstrated significant improvement in progression-free survival (PFS) with cabozantinib (Cabometyx) vs placebo in patients with advanced pancreatic or extra-pancreatic neuroendocrine tumors (NETs) following progression on prior systemic therapy. As such, the trial will be unblinded and discontinued following a unanimous decision from the Alliance for Clinical Trials in Oncology Independent Data and Safety Monitoring Board.¹

Adverse effects that occurred with cabozantinib in the trial were consistent with its known safety profile, and no new signals were reported. Detailed findings from the trial will be presented at an upcoming medical meeting and discussed with the FDA.

“As there is no standard of care for patients with advanced pancreatic or extrapancreatic neuroendocrine tumors whose disease has progressed after prior therapy, we are pleased to see that cabozantinib improved outcomes for two additional patient populations living with advanced, difficult-to-treat cancers,” Will Berg, MD, senior vice president, Medical Affairs, Exelixis, stated in a news release. “We are grateful for the recommendation of the Data and Safety Monitoring Board to unblind the CABINET study early due to a dramatic improvement in efficacy and look forward to discussing these findings with the US Food and Drug Administration.”

CABINET is a multicenter, randomized, double-blinded, placebo-controlled, pivotal phase 3 trial that enrolled 290 patients into 2 cohorts of patients with pancreatic NETs (n = 93) and extrapancreatic NETs (n = 197) in the United States.

To be eligible for enrollment, patients must have well or moderately differentiated, locally advanced unresectable or metastatic pancreatic or extra-pancreatic NETs by local pathology,² measurable disease per RECIST v1.1 criteria, and disease progression in the 12 months prior to enrollment after at least one FDA-approved line of therapy other than somatostatin analogs.

Prior therapy must have included either everolimus (Afinitor), sunitinib (Sutent), or lutetium Lu 177 dotatate (¹⁷⁷Lu dotatate; Lutathera) in patients with pancreatic NETs; everolimus in patients with lung NETs; and everolimus or ¹⁷⁷Lu dotatate in patients with gastrointestinal NETs.

Patients were randomly assigned 2:1 to receive oral cabozantinib once daily or placebo in 28-day cycles in each of the 2 cohorts.²

In addition to the primary end point of PFS in each cohort, secondary end points included overall survival, radiographic response rate, and safety. Following documentation of disease progression, patients were unblinded, and those receiving placebo were allowed to cross over to open-label therapy with cabozantinib.¹

“Patients with progressive neuroendocrine tumors have limited treatment options. At present, after progression on previous therapies, the treatment path is unclear, underscoring the need for additional options for this disease that is rising in incidence,” Jennifer Chan, MD, MPH, study chair for the CABINET trial and clinical director of the Gastrointestinal Cancer Center and director of the Program in Carcinoid and Neuroendocrine Tumors at Dana-Farber Cancer Institute, stated in the release. “These promising findings from the CABINET trial, in which cabozantinib showed an efficacy benefit for patients with pancreatic and extra-pancreatic neuroendocrine tumors, are welcome news and show the potential for cabozantinib to address important unmet needs for this community.”

References

1. Exelixis announces positive results from phase 3 CABINET pivotal trial evaluating cabozantinib in advanced pancreatic and extra-pancreatic neuroendocrine tumors. News release. Exelixis, Inc. August 24, 2023. Accessed August 24, 2023. https://ir.exelixis.com/news-releases/news-release-details/exelixis-announces-positive-results-phase-3-cabinet-pivotal
2. Testing cabozantinib in patients with advanced pancreatic neuroendocrine and carcinoid tumors. ClinicalTrials.gov. Updated August 21, 2023. Accessed August 24, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT03375320?term=a021602&draw=2&rank=1