DART (SWOG S1609): nivolumab plus ipilimumab in rare tumours

DART opened in January 2017 under SWOG for the NCI, co-led by Sandip Patel and Razelle Kurzrock, and is the largest immunotherapy basket in rare cancers, with more than 50 histology cohorts and close to 800 patients. Every cohort receives nivolumab with low-dose ipilimumab, and each is analysed separately for objective response with a two-stage rule, so an unpromising histology stops after the first stage while a promising one expands.

The first cohort to report, in Clinical Cancer Research in 2020, was neuroendocrine tumours: a quarter of patients responded, with responses concentrated in high-grade disease and none in low-grade tumours, which changed how oncologists think about immunotherapy in neuroendocrine carcinoma. Angiosarcoma followed in 2021 with responses in about a quarter of patients, strikingly in cutaneous tumours of the scalp and face. Other cohorts, including several sarcoma and gynaecological histologies, have reported little activity, and the trial has published analyses of tumour mutational burden and other correlates across cohorts.

DART is the practical proof that a basket run through the NCI's community oncology network can recruit rare cancers quickly, and its positive cohorts have entered guidelines as options where nothing else exists. What remains open is whether cohorts of 20 to 30 patients without a control can carry regulatory weight, and which rare histologies deserve a confirmatory trial.