Phase II open-label study of S-588410 as maintenance monotherapy after first-line platinum-containing chemotherapy in patients with advanced or metastatic urothelial carcinoma.

440 Background: S-588410 is a cancer peptide vaccine composed of 5 human leukocyte antigen (HLA)-A*24:02-restricted epitope peptides derived from 5 cancer-testis antigens: DEPDC1, MPHOSPH1, URLC10, CDCA1 and KOC1; all of which are highly expressed in urothelial carcinoma. This study aimed to evaluate the effect of S-588410 maintenance therapy on peptide-specific cytotoxic T-lymphocyte (CTL) induction in patients with advanced or metastatic urothelial carcinoma after first-line platinum-based chemotherapy. Methods: An open-label, multicenter phase II trial was performed across 62 sites in Japan, the United Kingdom, France and Bulgaria (EudraCT 2013-005274-22). Eligible patients had completed ≥4 cycles of first-line platinum-based chemotherapy without disease progression. HLA-A*24:02-positive patients received S-588410 (1 mg of each of 5 peptides mixed with Montanide ISA 51 VG) subcutaneously weekly for 12 weeks, then every 2 weeks for up to 2 years. HLA-A*24:02-negative patients were enrolled in an observation group and did not receive study drug. The primary endpoint for the S-588410 group was the CTL induction rate at 12 weeks, defined as the proportion of patients who showed increased CTL activity for ≥1 peptide. Secondary endpoints included CTL induction rate after 1 year, antitumor effect defined by immune-related response criteria, progression-free survival (PFS), overall survival (OS), and safety. Results: A total of 81 patients with platinum-sensitive advanced or metastatic urothelial carcinoma were enrolled (S-588410 group, n=45; observation group, n=36) between April 2014 and November 2017. Most patients were male and Asian with a mean age of 67 years. CTLs were induced in 42 (93.3%) patients who received S-588410 for 12 weeks (P<0.0001, one-sided binomial test where the CTL induction rate is ≤50% as the null hypothesis). The CTL induction rate steadily increased to 95.6% within 48 weeks. CTL activity was high for the DEPDC1, MPHOSPH1 and URLC10 peptides. The response rate (immune-related complete response [CR] or partial response [PR]) was 8.9% (4/45 patients) in the S-588410 group and 0% in the observation group. Tumor imaging showed gradual (PR, n=3) and durable (CR, n=1) tumor shrinkage after ≥36 weeks in the S-588410 group. Median PFS was 18.1 weeks in the S-588410 group and 12.5 weeks in the observation group. Median OS was 71 and 99 weeks, respectively. The most frequent treatment-emergent adverse event was injection site reaction (42/45 patients [93.3%]; Grades 1–3). Pyrexia, rash and pruritus were also observed in the S-588410 group, but not the observation group. Conclusions: S-588410 showed a potent immune response and acceptable safety profile in patients with advanced or metastatic urothelial carcinoma, potentially offering a clinical benefit as post-chemotherapy maintenance therapy. Clinical trial information: EudraCT 2013-005274-22.