2502 Background: Rare tumors are underrepresented in clinical trials, though they collectively comprise an estimated 22% of all cancer cases. The NCI/SWOG S1609 trial evaluated efficacy signals across 53 rare cancer cohorts treated with dual CTLA-4 and PD-1 inhibition. Methods: A prospective, open-label, multicenter phase 2 trial of ipilimumab (1mg/kg intravenously every 6 weeks) plus nivolumab (240mg intravenously every 2 weeks) was conducted from 1/13/2017 to 3/15/2023. A statistical framework was established to evaluate each cohort in a two-stage design. The primary end point was objective response rate (ORR); progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR, ORR + stable disease >6 months), i-outcomes, and toxicity were secondary and exploratory endpoints. Results: 798 patients were enrolled and 727 eligible patients received treatment. 1,083 national (USA) sites opened the trial. Median (range) patient age was 60 (18-88) years; 344 (47%) patients were male. 24 of 53 cohorts (45%) demonstrated clinical activity, defined as ≥2 patients with confirmed response. Median (range) ORR was 12% (0-75%); CBR, 27% (0-75%). Median (range) 2-year PFS was 10% (0-75%); 3-year OS was 23% (0-100%). 6-month PFS was moderately correlated with 1- and 3-year OS (R 2 =0.61 and 0.54, respectively). Patients who attained an iOR versus OR had similar OS. 82 patients (11%) had iPFS ≥2 years. Treatment-related adverse events (AEs) of any cause and immune-mediated occurred in 603 (82.9%) and 465 (64.0%) patients. AEs led to treatment discontinuation in 102 patients (14.0%). Most common AEs were fever (38.1%), diarrhea (21.2%), and rash/pruritis (19.3%). 13 patients (1.8%) experienced treatment-related grade 5 AEs. Patients alive at 6 months who discontinued treatment due to immune-related AE had longer OS than those who discontinued for other reasons (p = 0.021). Conclusions: Patients with multiple rare cancer types derived meaningful response to ipilimumab plus nivolumab. Characterization of biologically defined subsets is underway to optimize therapeutic selection. Clinical trial information: NCT02834013 . Response among all cohorts and cohorts with iRECIST iClinical benefit rate (iORR+iSD>6 mos) ≥50%. Cohort N iConfirmed response iClinical benefit iCR iPR 6-month iPFS 2-year iPFS 1-year OS 3-year OS Median iPFS (months) All 727 13% 29% 3% 10% 30% 12% 48% 24% 2.2 Gestational trophoblastic disease 4 75% 75% 25% 50% 75% 75% 100% 100% Not Reached Basal cell carcinoma 17 35% 71% 0 35% 76% 24% 76% 53% 12.1 Chordoma 10 0 70% 0 0 80% 30% 80% 30% 13.1 Bronchoalveolar carcinoma lung 8 25% 62%
Patel et al. (Wed,) studied this question.