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Abstract：
BACKGROUND: Effective maintenance therapy for urothelial carcinoma (UC) is needed to delay progression after first-line chemotherapy.
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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).
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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).
摘要：
背景：尿路上皮癌（UC）需要有效的维持治疗以延迟一线化疗后的进展。
目的：评估S-588410，一种含有5种人白细胞抗原（HLA）-A*24:02-限制性表位肽的癌症肽疫苗，该肽来自5种癌症睾丸抗原（DEPDC1，MPHOSPH1，URLC10，CDCA1和KOC1），临床稳定的晚期或转移性UC患者。
方法：这个开放标签，国际,2期试验纳入已完成≥4个周期一线含铂化疗且无疾病进展的UC患者.45名HLA-A*24：02阳性患者每周皮下注射S-588410（MontanideISA51VG，每种肽1mg/mL），持续12周，然后每2周一次，持续24个月。36例HLA-A*24:02阴性患者未接受S-588410（观察组）。主要终点是12周时针对≥1种肽的细胞毒性T淋巴细胞（CTL）诱导率。
结果：S-588410组的CTL诱导率为93.3％（p<0.0001，单侧二项检验，率≤50％为零假设）。S-588410组的抗肿瘤反应率为8.9％，观察组为0％；中位无进展生存期为18.1和12.5周，中位总生存期为71.0和99.0周，分别。最常见的治疗引起的不良事件是注射部位反应（47个事件，1-3级）在93.3%（n=42/45）的参与者中报告。
结论：S-588410显示出高CTL诱导率，可接受的安全概况，和适度的临床反应，作为接受铂类一线化疗的晚期或转移性UC参与者的维持治疗(EudraCT2013-005274-22).
目的：评估S-588410，一种含有5种人白细胞抗原（HLA）-A*24:02-限制性表位肽的癌症肽疫苗，该肽来自5种癌症睾丸抗原（DEPDC1，MPHOSPH1，URLC10，CDCA1和KOC1），临床稳定的晚期或转移性UC患者。
方法：这个开放标签，国际,2期试验纳入已完成≥4个周期一线含铂化疗且无疾病进展的UC患者.45名HLA-A*24：02阳性患者每周皮下注射S-588410（MontanideISA51VG，每种肽1mg/mL），持续12周，然后每2周一次，持续24个月。36例HLA-A*24:02阴性患者未接受S-588410（观察组）。主要终点是12周时针对≥1种肽的细胞毒性T淋巴细胞（CTL）诱导率。
结果：S-588410组的CTL诱导率为93.3％（p<0.0001，单侧二项检验，率≤50％为零假设）。S-588410组的抗肿瘤反应率为8.9％，观察组为0％；中位无进展生存期为18.1和12.5周，中位总生存期为71.0和99.0周，分别。最常见的治疗引起的不良事件是注射部位反应（47个事件，1-3级）在93.3%（n=42/45）的参与者中报告。
结论：S-588410显示出高CTL诱导率，可接受的安全概况，和适度的临床反应，作为接受铂类一线化疗的晚期或转移性UC参与者的维持治疗(EudraCT2013-005274-22).
