A Phase 2 Study of S-588410 Maintenance Monotherapy for Platinum-Treated Advanced or Metastatic Urothelial Carcinoma

Author:

Shimizu Nobuaki1,Hussain Syed A.2,Obara Wataru3,Yamasaki Toshinari4,Takashima Satoru5,Hasegawa Takahiro6,Iguchi Motofumi7,Igarashi Kenji8,Ogawa Osamu4,Fujioka Tomoaki3

Affiliation:

1. Department of Urology, Gunma Prefectural Cancer Center, Ota, Gunma, Japan

2. The Clatterbridge Cancer Centre, Wirral, UK

3. Department of Urology, Iwate Medical University, Morioka, Iwate, Japan

4. Department of Urology, Kyoto University Graduate School of Medicine, Kyoto, Japan

5. Clinical Development, Shionogi & Co., Ltd., Osaka, Japan

6. Biostatistics Center, Shionogi & Co., Ltd., Osaka, Japan

7. Medical Affairs, Shionogi & Co., Ltd., Osaka, Japan

8. Project Management, Shionogi & Co., Ltd., Osaka, Japan

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. MATERIALS AND 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).

Publisher

IOS Press

Subject

Urology,Oncology

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