Data from the phase 2 DART trial, presented at the American Association for Cancer Research Annual Meeting, revealed patients with rare, high-grade neuroendocrine tumors derived clinical benefit from a combination of the immune checkpoint inhibitors ipilimumab and nivolumab.
The open label DART trial, managed by Southwest Oncology Group, utilizes a “basket” design that allows for testing of a single drug or drug combination in various tumor types. DART is currently testing the immunotherapy combination of ipilimumab (Yervoy, Bristol-Myers Squibb) and nivolumab (Opdivo, Bristol-Myers Squibb) in patients with 37 types of rare cancers, which account for nearly a quarter of all cancers diagnosed worldwide.
Sandip Patel, MD, associate professor of medicine at UC San Diego School of Medicine and medical oncologist with Moores Cancer Center at US San Diego Health, and his colleagues evaluated the combination in 33 patients with neuroendocrine tumors, including 19 patients (58%) with high-grade disease, who had a median two lines of prior therapy. Most of the tumors were in the gastrointestinal tract (n= 15) or the lungs (n = 6). Patients received 1 mg/kg ipilimumab every 6 weeks and 240 mg IV nivolumab every 2 weeks.
The primary endpoint of the study is overall response rate (ORR), with progression free survival (PFS), overall survival (OS), stable disease for more than 6 months and toxicity as secondary endpoints.
Results showed an ORR of 24%, including one complete response and seven partial responses, all of which were among patients with high-grade neuroendocrine tumors. One-third of all patients (n = 11) had stable disease, including two patients with stable disease for more than 6 months. Both of those patients had low/intermediate-grade disease. The 6-month PFS was 30% and median OS was 11 months. The most common toxicities were fatigue (30%) and nausea (27%). The most frequent immune-related adverse event was grade 3 to grade 4 alanine aminotransferase elevation (9%). No grade 5 toxicities occurred.
The DART trial commenced in 2017 and has enrolled over 550 patients. Enrollment is currently open at more than 800 cancer and community centers across the U.S.
About neuroendocrine tumors
A neuroendocrine tumor (NET) is a rare type of tumor that arises from specialized body cells called neuroendocrine cells. These cells have traits of both nerve cells and hormone-producing cells, and release hormones into the blood in response to signals from the nervous system. Because a neuroendocrine tumor arises from cells that produce hormones, the tumor can also produce hormones. Neuroendocrine tumors can develop anywhere in the body, but most occur in the digestive tract, pancreas, rectum, lungs, or appendix.
Ipilimumab is a cytotoxic T-lymphocyte–associated antigen 4 [CTLA-4] checkpoint inhibitor. It has been approved by the FDA for melanoma. Ipilimumab is manufactured by Bristol-Myers Squibb and is marketed as Yervoy.
Nivolumab is a programmed death 1 [PD-1] checkpoint inhibitor. It has been approved by the FDA alone and in combination for a variety of cancers. Nivolumab is manufactured by Bristol-Myers Squibb and marketed as Opdivo.