Shimizu Nobuaki, Hussain Syed A, Obara Wataru, Yamasaki Toshinari, Takashima Satoru, Hasegawa Takahiro, Iguchi Motofumi, Igarashi Kenji, Ogawa Osamu, Fujioka Tomoaki
Department of Urology, Gunma Prefectural Cancer Center, Ota, Gunma, Japan.
The Clatterbridge Cancer Centre, Wirral, UK.
Bladder Cancer. 2022 Jun 3;8(2):179-192. doi: 10.3233/BLC-211592. eCollection 2022.
Effective maintenance therapy for urothelial carcinoma (UC) is needed to delay progression after first-line chemotherapy.
To evaluate S-588410, a cancer peptide vaccine containing five human leukocyte antigen (HLA)-A24:02-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.
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-A24:02-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-A24:02-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.
The CTL induction rate in the S-588410 group was 93.3% ( < 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% ( = 42/45) of participants.
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).
需要有效的尿路上皮癌（UC）维持治疗来延缓一线化疗后的疾病进展。
评估S-588410，一种癌症肽疫苗，其包含五种源自五种癌胚抗原（DEPDC1、MPHOSPH1、URLC10、CDCA1和KOC1）的人白细胞抗原（HLA）-A24:02限制性表位肽，用于接受化疗且病情临床稳定的晚期或转移性UC患者。
这项开放标签、国际性2期试验纳入了已完成≥4个周期一线含铂化疗且无疾病进展的UC患者。45名HLA-A24:02阳性患者每周皮下注射S-588410（含1mg/mL各肽的Montanide ISA 51 VG），共12周，之后每2周注射一次，最长持续24个月。36名HLA-A24:02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。
S-588410组的CTL诱导率为93.3%（<0.0001，以≤50%的发生率作为原假设的单侧二项式检验）。S-588410组的抗肿瘤反应率为8.9%，观察组为0%；无进展生存期的中位数分别为18.1周和12.5周，总生存期的中位数分别为71.0周和99.0周。最常见的治疗中出现的不良事件是注射部位反应（47例事件，1-3级），93.3%（=42/45）的参与者报告了该反应。
作为接受一线铂类化疗的晚期或转移性UC患者的维持治疗，S-588410表现出高CTL诱导率、可接受的安全性和适度的临床反应（欧洲临床试验数据库编号2013-005274-22）。
