Related Experiment Video
Updated: Jul 7, 2026
Methods for Evaluating the Role of c-Fos and Dusp1 in Oncogene Dependence
Published on: January 7, 2019
DART (NCI/SWOG S1609): comprehensive final results from dual checkpoint inhibition with CTLA-4 and PD-1 blockade in
Background:
We summarize final results of the NCI/SWOG S1609 trial, the objective of which was to evaluate efficacy signals across 53 refractory rare cancer cohorts treated with dual cytotoxic T-lymphocyte-associated antigen 4 and programmed cell death protein 1 inhibition.
Patients And Methods:
A prospective, open-label, multicenter phase II trial of ipilimumab (1 mg/kg intravenously every 6 weeks) plus nivolumab (240 mg intravenously every 2 weeks) was conducted (N = 53 cohorts). A statistical framework was established to evaluate each cohort in a two-stage design. The primary endpoint was objective response rate (ORR), with progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR, ORR plus stable disease >6 months), immune-related (i)-outcomes, and toxicity as secondary and exploratory endpoints.
Results:
Overall, 798 previously treated patients were enrolled onto S1609/Dual Anti-CTLA-4 and Anti-PD-1 blockade in Rare Tumors (DART); 727 eligible patients received treatment; 1083 national (United States) sites opened the trial. Twenty-four of 53 cohorts (45%) demonstrated clinical activity, defined as ≥2 patients with confirmed response. Median (range) ORR was 12% (0%-75%); CBR was 27% (0%-75%). Median (range) 2-year PFS was 10% (0%-75%); 3-year OS was 23% (0%-100%). PFS at 6 months was moderately correlated with 1- and 3-year OS. Patients who attained an iOR versus OR had similar OS. Altogether, 82 patients (11% of the 727 enrolled patients) had an iPFS of ≥2 years. i-toxicity rates were comparable with those reported in prior studies. Adverse events led to treatment discontinuation in 102 patients (14%). The most common adverse events were fever, diarrhea, and rash/pruritus. Patients alive at 6 months who discontinued treatment due to i-toxicity had longer OS than those who discontinued treatment for other reasons.
Conclusion:
Patients with multiple refractory rare cancer types derived meaningful response to ipilimumab plus nivolumab treatment. More robust characterization of biologically defined subsets is underway to optimize therapeutic selection.
Insights
Dual ipilimumab and nivolumab immunotherapy showed efficacy in rare refractory cancers. Patients experienced meaningful responses, with ongoing research to optimize treatment selection for better outcomes.
Area of Science:
- Oncology
- Immunotherapy
- Clinical Trials
Background:
- NCI/SWOG S1609 trial evaluated dual CTLA-4 and PD-1 inhibition in rare cancers.
- Focused on 53 refractory rare cancer cohorts.
Purpose of the Study:
- To assess efficacy signals of ipilimumab plus nivolumab in rare refractory cancers.
- Primary endpoint was objective response rate (ORR).
Main Methods:
- Prospective, open-label, multicenter phase 2 trial.
- 53 cohorts treated with ipilimumab and nivolumab.
- Two-stage design with ORR, PFS, OS, CBR, and toxicity as endpoints.
Main Results:
- 45% of cohorts showed clinical activity.
- Median ORR was 12%, median CBR was 27%.
- 11% of patients achieved ≥2 years progression-free survival (PFS); immune-related toxicity was comparable to prior studies.
Conclusions:
- Ipilimumab plus nivolumab demonstrated meaningful responses in rare refractory cancers.
- Further characterization of subsets is needed for optimized therapeutic selection.
