Alliance presents detailed results from phase III CABINET pivotal Trial evaluating cabozantinib in advanced neuroendocrine tumors at ESMO 2023

The Alliance for Clinical Trials in Oncology today announced detailed results will be presented at ESMO 2023 from CABINET (A021602), a phase III pivotal trial evaluating cabozantinib compared with placebo in two cohorts of patients with previously treated neuroendocrine tumors: one cohort of patients with advanced pancreatic neuroendocrine tumors (pNET) and a second cohort of patients with advanced extra-pancreatic NET (epNET). The study met the primary objective for each cohort, demonstrating that cabozantinib provided dramatic improvements in median progression-free survival (PFS) for the patients in the pNET and epNET cohorts. The data are being presented today at 2:30 am ET/8:30 am CEST during the Proffered Paper Session – NETs and Endocrine Tumours at the 2023 European Society of Medical Oncology (ESMO) Congress (LBA53) by Alliance Study Chair Jennifer Chan, MD, MPH.

“Although progress has been made in recent years, there remains a critical need for new and effective therapies for patients with advanced neuroendocrine tumors. Given that there is no standard treatment for patients with progressive disease, these results showing notable improvements in progression-free survival are highly encouraging for patients and their physicians,” said Dr. Chan, Clinical Director of the Gastrointestinal Cancer Center and Director of the Program in Carcinoid and Neuroendocrine Tumors at Dana-Farber Cancer Institute. “I am pleased to present these important findings at ESMO today, as they underscore the potential of cabozantinib as a much-needed new treatment option for this disease, which is rising in incidence.”

In August, the Alliance Data and Safety Monitoring Board (DSMB) recommended the study stop and be unblinded early due to the dramatic improvement in efficacy observed at an interim analysis. The DSMB based their vote on data from interim analyses of PFS using local radiology assessments. Ancillary analyses were conducted using local and central assessments of patients enrolled through June 2023.

Results from the CABINET study presented today at ESMO demonstrate that treatment with cabozantinib resulted in compelling improvements in PFS based both on local review and on independent blinded central radiology review. At a median follow-up of 13.9 months, the median PFS for patients with epNET who took cabozantinib was 8.3 months, compared to 3.2 months for those who took a placebo. At a median follow-up of 16.7 months, patients with pNET who took cabozantinib had a median PFS of 11.4 months, compared to 3 months for those who took a placebo.

The safety profile of cabozantinib observed in each cohort was consistent with those found in other studies of the drug. These include hypertension, fatigue, diarrhea, and skin rash. No new safety signals were identified.

For patients with advanced NET, treatment options include somatostatin analogs (SSAs), targeted therapy, Lu-177 dotatate, which is a form of peptide-receptor radionuclide therapy (PRRT), or chemotherapy. More than half of patients in each cohort received prior everolimus or prior Lu-177 dotatate.

“The CABINET trial is a great example of the importance of the National Clinical Trials Network, sponsored by the National Cancer Institute, in conducting rigorous, practice changing trials at both academic and community oncology practices throughout the United States, working with industry partners, patient advocacy, and academia,” noted Eileen O’Reilly, MD, from Memorial Sloan Kettering Cancer Center and Jeffrey Meyerhardt, MD, MPH, from Dana-Farber Cancer Institute, who co-chair the Gastrointestinal Committee for the Alliance.

CABINET (randomized, double-blinded phase III study of CABozantinib versus placebo In patients with advanced NEuroendocrine Tumors after progression on prior therapy) is a multicenter, randomized, double-blinded, placebo-controlled phase III pivotal trial. As of June 2023, this trial enrolled 290 patients in two separate cohorts (pNET, n=93; epNET, n=197) in the United States and were included in the analyses reviewed by the Alliance DSMB. Patients were randomized 2:1 into the cabozantinib or placebo arms of the study in each of the two cohorts. Patients must have had measurable disease per RECIST 1.1 criteria and must have experienced disease progression after at least one FDA-approved line of prior therapy other than somatostatin analogs. The primary endpoint was PFS in each cohort. Upon confirmation of disease progression, patients were unblinded, and those receiving placebo were permitted to cross over to open-label therapy with cabozantinib. Secondary endpoints included overall survival, radiographic response rate and safety.

CABINET 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 (NCTN) as part of Exelixis’ collaboration with the National Cancer Institute’s Cancer Therapy Evaluation Program (NCI-CTEP). To learn more about the CABINET trials, visit ClinicalTrials.gov.

Follow the meeting live on X (formerly known as Twitter) using the hashtag #ESMO23 and follow the Alliance on X (formerly known as Twitter) at @ALLIANCE_org.

# # #

Reference: Alliance A021602: Randomized, double-blinded phase III study of cabozantinib versus placebo in patients with advanced neuroendocrine tumors after progression on prior therapy (CABINET). A full description of this clinical trial can be found at https://classic.clinicaltrials.gov/ct2/show/NCT03375320.

The Alliance for Clinical Trials in Oncology develops and conducts clinical trials with promising new cancer therapies, and utilizes the best science to develop optimal treatment and prevention strategies for cancer, as well as research methods to alleviate side effects of cancer and cancer treatments. The Alliance is part of the National Clinical Trials Network (NCTN) funded by the National Cancer Institute (NCI) and serves as a research base for the NCI Community Research Oncology Program (NCORP). The Alliance comprises nearly 10,000 cancer specialists at hospitals, medical centers, and community clinics across the United States and Canada. To learn more, visit www.AllianceforClinicalTrialsinOncology.org.