Results for the cohort of patients with rare neuroendocrine tumors receiving combination immune checkpoint blockade therapy (ie, nivolumab plus ipilimumab) in the nonrandomized, phase 2, Southwest Oncology Group (SWOG) S1609 basket trial, also referred to as the Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART) trial (ClinicalTrial.gov Identifiers: NCT02834013; NCT03420521), showed a high overall response rate (ORR) for those with high-grade tumors.1-2 The findings from this study were presented at the American Association for Cancer (AACR) Annual Meeting 2019.1
More specifically, the rare neuroendocrine tumor cohort of the DART trial enrolled patients with histologically confirmed advanced, progressive, well-differentiated nonfunctional neuroendocrine tumors of the pancreas, lung, or gastrointestinal (GI) tract to receive the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitor, ipilimumab, at a dose of 1mg/kg intravenously (IV) over 30 minutes every 6 weeks, and the programmed cell death 1 (PD-1) inhibitor, nivolumab, at a dose of 240 mg IV over 60 minutes every 2 weeks until disease progression or unacceptable toxicity occurred.
The primary objective of the DART trial is the determination of ORR by RECIST v1.1 criteria. Secondary objectives include safety, progression-free survival (PFS), overall survival (OS), immune-related PFS, and immune-related OS.
Of the 33 patients included in the neuroendocrine cohort of the DART trial, most had tumors of the GI tract or the lungs, and 19 had high-grade disease.
In the overall cohort of patients with neuroendocrine disease, 70% developed progressive disease within 6 months, and median OS was at least 11 months.
Interestingly, 42% of patients with high-grade neuroendocrine disease and 0% of patients with low-grade neuroendocrine disease achieved a partial or complete response to treatment.
“These early results are really encouraging — and intriguing,” according to Sandip Patel, MD, the DART clinical study chair, who is an associate professor of medicine at the University of California at San Diego School of Medicine, and a medical oncologist with Moores Cancer Center at UC San Diego Health. “We found a clear difference in response to treatment between the high-grade and low-grade forms of this cancer type. So tumor biology makes a difference. We don’t yet know why, but we’ve opened another treatment arm of the trial to patients with just high-grade neuroendocrine carcinoma to see if we see the same response to the immunotherapy combination.”2
Currently, the ongoing DART trial is being conducted at over 800 hospitals, cancer centers, and community clinics across the US, and has enrolled over 550 patients into 37 rare tumor cohorts.
- Sandip PP, OthusM, ChaeYK, et al. A phase II basket trial of dual anti-CTLA-4 and anti-PD-1 blockade in rare tumors (DART) S1609: The neuroendocrine cohort. Presentation at: American Association for Cancer Research (AACR) Annual Meeting 2019; March 29-April 3, 2019; Atlanta, Georgia. Abstract CT039.
- SWOG Cancer Network. Immunotherapy combination effective for patients with rare neuroendocrine cancer. Published March 31, 2019. Accessed March 31, 2019.