%0 Journal Article
%T A Phase 2 Study of S-588410 Maintenance Monotherapy for Platinum-Treated Advanced or Metastatic Urothelial Carcinoma.
%A Shimizu N
%A Hussain SA
%A Obara W
%A Yamasaki T
%A Takashima S
%A Hasegawa T
%A Iguchi M
%A Igarashi K
%A Ogawa O
%A Fujioka T
%J Bladder Cancer
%V 8
%N 2
%D 2022
%M 38993370
%F 1.449
%R 10.3233/BLC-211592
%X <B>BACKGROUND: </B>Effective maintenance therapy for urothelial carcinoma (UC) is needed to delay progression after first-line chemotherapy.<BR><B>OBJECTIVE: </B>To evaluate S-588410, a cancer peptide vaccine containing five human leukocyte antigen (HLA)-A*24:02-restricted epitope peptides derived from five cancer-testis antigens (DEPDC1, MPHOSPH1, URLC10, CDCA1, and KOC1) in chemotherapy-treated, clinically stable patients with advanced or metastatic UC.<BR><B>METHODS: </B>This open-label, international, phase 2 trial enrolled patients with UC who had completed≥4 cycles of first-line platinum-containing chemotherapy without disease progression. Forty-five HLA-A*24:02-positive patients received subcutaneous injections of S-588410 (Montanide ISA 51 VG with 1 mg/mL of each peptide) weekly for 12 weeks then once every 2 weeks thereafter for up to 24 months. Thirty-six HLA-A*24:02-negative patients did not receive S-588410 (observation group). The primary endpoint was the rate of cytotoxic T-lymphocyte (CTL) induction against≥1 of the peptides at 12 weeks.<BR><B>RESULTS: </B>The CTL induction rate in the S-588410 group was 93.3% (p < 0.0001, one-sided binomial test with a rate of≤50% as the null hypothesis). The antitumor response rate was 8.9% in the S-588410 group and 0% in the observation group; median progression-free survival was 18.1 versus 12.5 weeks and median overall survival was 71.0 versus 99.0 weeks, respectively. The most frequent treatment-emergent adverse event was injection-site reactions (47 events, grades 1-3) reported in 93.3% (n = 42/45) of participants.<BR><B>CONCLUSIONS: </B>S-588410 demonstrated a high CTL induction rate, acceptable safety profile, and modest clinical response, as maintenance therapy in participants with advanced or metastatic UC who had received first-line platinum-based chemotherapy (EudraCT 2013-005274-22).