A phase I/II study of cancer peptide vaccine S-288310 in patients with advanced urothelial carcinoma of the bladder

W. Obara, Masatoshi Eto, H. Mimata, K. Kohri, N. Mitsuhata, I. Miura, T. Shuin, T. Miki, T. Koie, H. Fujimoto, K. Minami, Y. Enomoto, T. Nasu, T. Yoshida, H. Fuse, I. Hara, K. Kawaguchi, A. Arimura, T. Fujioka

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Background: S-288310, a cancer peptide vaccine composed of two HLA-A*24:02-restricted peptides derived from two oncoantigens, DEP domain-containing 1 (DEPDC1) and M-phase phosphoprotein 1 (MPHOSPH1), was investigated in urothelial carcinoma (UC) of the bladder. Patients and methods: Thirty eight HLA-A*24:02-positive patients with progressive UC were enrolled in this study. In the phase I part of the study, three patients each were treated with S-288310 at 1mg or 2 mg/peptide subcutaneously once a week to evaluate safety and tolerability. In the phase II, 32 patients were randomized to receive either 1mg or 2mg to evaluate the difference in cytotoxic T lymphocytes (CTL) induction and safety. Results: S-288310 was safe and well tolerated in the phase I. Of 27 patients evaluable for immune responses in the phase II, there was no difference in CTL induction rate between the 1mg (100%) and 2mg (80.0%) groups. Of 32 patients receiving S-288310 in the phase II, the most frequent drug-related AE was the injection site reaction that was observed in 29 patients (90.6%), but none of the patients discontinued administration due to these reactions and no dose relationship in the frequency and severity was observed. The objective response rate of the 32 patients was 6.3% and the disease control rate was 56.3%. The median overall survival (OS) rates for patients vaccinated with S-288310 after one regimen of chemotherapy, 2 regimens, or 3 or more were 14.4, 9.1 and 3.7 months, respectively, and 32.2% of patients post first-line treatment were alive at 2 years. OS of patients who showed CTL induction to both peptides was longer than that of those with CTL induction to no or one peptide. Conclusion: S-288310 was well-tolerated and effectively induced peptide-specific CTLs, which were correlated with longer survival for patients with UC of the bladder. Trial registration ID: JapicCTI-090980

Original languageEnglish
Pages (from-to)798-803
Number of pages6
JournalAnnals of Oncology
Volume28
Issue number4
DOIs
Publication statusPublished - Apr 1 2017
Externally publishedYes

Fingerprint

Cancer Vaccines
Subunit Vaccines
Urinary Bladder
Carcinoma
Cytotoxic T-Lymphocytes
Peptides
Safety
Survival
Phosphoproteins
Cell Division

All Science Journal Classification (ASJC) codes

  • Hematology
  • Oncology

Cite this

A phase I/II study of cancer peptide vaccine S-288310 in patients with advanced urothelial carcinoma of the bladder. / Obara, W.; Eto, Masatoshi; Mimata, H.; Kohri, K.; Mitsuhata, N.; Miura, I.; Shuin, T.; Miki, T.; Koie, T.; Fujimoto, H.; Minami, K.; Enomoto, Y.; Nasu, T.; Yoshida, T.; Fuse, H.; Hara, I.; Kawaguchi, K.; Arimura, A.; Fujioka, T.

In: Annals of Oncology, Vol. 28, No. 4, 01.04.2017, p. 798-803.

Research output: Contribution to journalArticle

Obara, W, Eto, M, Mimata, H, Kohri, K, Mitsuhata, N, Miura, I, Shuin, T, Miki, T, Koie, T, Fujimoto, H, Minami, K, Enomoto, Y, Nasu, T, Yoshida, T, Fuse, H, Hara, I, Kawaguchi, K, Arimura, A & Fujioka, T 2017, 'A phase I/II study of cancer peptide vaccine S-288310 in patients with advanced urothelial carcinoma of the bladder', Annals of Oncology, vol. 28, no. 4, pp. 798-803. https://doi.org/10.1093/annonc/mdw675
Obara, W. ; Eto, Masatoshi ; Mimata, H. ; Kohri, K. ; Mitsuhata, N. ; Miura, I. ; Shuin, T. ; Miki, T. ; Koie, T. ; Fujimoto, H. ; Minami, K. ; Enomoto, Y. ; Nasu, T. ; Yoshida, T. ; Fuse, H. ; Hara, I. ; Kawaguchi, K. ; Arimura, A. ; Fujioka, T. / A phase I/II study of cancer peptide vaccine S-288310 in patients with advanced urothelial carcinoma of the bladder. In: Annals of Oncology. 2017 ; Vol. 28, No. 4. pp. 798-803.
@article{679fa322f41f43c6ad2aab7eed8de089,
title = "A phase I/II study of cancer peptide vaccine S-288310 in patients with advanced urothelial carcinoma of the bladder",
abstract = "Background: S-288310, a cancer peptide vaccine composed of two HLA-A*24:02-restricted peptides derived from two oncoantigens, DEP domain-containing 1 (DEPDC1) and M-phase phosphoprotein 1 (MPHOSPH1), was investigated in urothelial carcinoma (UC) of the bladder. Patients and methods: Thirty eight HLA-A*24:02-positive patients with progressive UC were enrolled in this study. In the phase I part of the study, three patients each were treated with S-288310 at 1mg or 2 mg/peptide subcutaneously once a week to evaluate safety and tolerability. In the phase II, 32 patients were randomized to receive either 1mg or 2mg to evaluate the difference in cytotoxic T lymphocytes (CTL) induction and safety. Results: S-288310 was safe and well tolerated in the phase I. Of 27 patients evaluable for immune responses in the phase II, there was no difference in CTL induction rate between the 1mg (100{\%}) and 2mg (80.0{\%}) groups. Of 32 patients receiving S-288310 in the phase II, the most frequent drug-related AE was the injection site reaction that was observed in 29 patients (90.6{\%}), but none of the patients discontinued administration due to these reactions and no dose relationship in the frequency and severity was observed. The objective response rate of the 32 patients was 6.3{\%} and the disease control rate was 56.3{\%}. The median overall survival (OS) rates for patients vaccinated with S-288310 after one regimen of chemotherapy, 2 regimens, or 3 or more were 14.4, 9.1 and 3.7 months, respectively, and 32.2{\%} of patients post first-line treatment were alive at 2 years. OS of patients who showed CTL induction to both peptides was longer than that of those with CTL induction to no or one peptide. Conclusion: S-288310 was well-tolerated and effectively induced peptide-specific CTLs, which were correlated with longer survival for patients with UC of the bladder. Trial registration ID: JapicCTI-090980",
author = "W. Obara and Masatoshi Eto and H. Mimata and K. Kohri and N. Mitsuhata and I. Miura and T. Shuin and T. Miki and T. Koie and H. Fujimoto and K. Minami and Y. Enomoto and T. Nasu and T. Yoshida and H. Fuse and I. Hara and K. Kawaguchi and A. Arimura and T. Fujioka",
year = "2017",
month = "4",
day = "1",
doi = "10.1093/annonc/mdw675",
language = "English",
volume = "28",
pages = "798--803",
journal = "Annals of Oncology",
issn = "0923-7534",
publisher = "Oxford University Press",
number = "4",

}

TY - JOUR

T1 - A phase I/II study of cancer peptide vaccine S-288310 in patients with advanced urothelial carcinoma of the bladder

AU - Obara, W.

AU - Eto, Masatoshi

AU - Mimata, H.

AU - Kohri, K.

AU - Mitsuhata, N.

AU - Miura, I.

AU - Shuin, T.

AU - Miki, T.

AU - Koie, T.

AU - Fujimoto, H.

AU - Minami, K.

AU - Enomoto, Y.

AU - Nasu, T.

AU - Yoshida, T.

AU - Fuse, H.

AU - Hara, I.

AU - Kawaguchi, K.

AU - Arimura, A.

AU - Fujioka, T.

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Background: S-288310, a cancer peptide vaccine composed of two HLA-A*24:02-restricted peptides derived from two oncoantigens, DEP domain-containing 1 (DEPDC1) and M-phase phosphoprotein 1 (MPHOSPH1), was investigated in urothelial carcinoma (UC) of the bladder. Patients and methods: Thirty eight HLA-A*24:02-positive patients with progressive UC were enrolled in this study. In the phase I part of the study, three patients each were treated with S-288310 at 1mg or 2 mg/peptide subcutaneously once a week to evaluate safety and tolerability. In the phase II, 32 patients were randomized to receive either 1mg or 2mg to evaluate the difference in cytotoxic T lymphocytes (CTL) induction and safety. Results: S-288310 was safe and well tolerated in the phase I. Of 27 patients evaluable for immune responses in the phase II, there was no difference in CTL induction rate between the 1mg (100%) and 2mg (80.0%) groups. Of 32 patients receiving S-288310 in the phase II, the most frequent drug-related AE was the injection site reaction that was observed in 29 patients (90.6%), but none of the patients discontinued administration due to these reactions and no dose relationship in the frequency and severity was observed. The objective response rate of the 32 patients was 6.3% and the disease control rate was 56.3%. The median overall survival (OS) rates for patients vaccinated with S-288310 after one regimen of chemotherapy, 2 regimens, or 3 or more were 14.4, 9.1 and 3.7 months, respectively, and 32.2% of patients post first-line treatment were alive at 2 years. OS of patients who showed CTL induction to both peptides was longer than that of those with CTL induction to no or one peptide. Conclusion: S-288310 was well-tolerated and effectively induced peptide-specific CTLs, which were correlated with longer survival for patients with UC of the bladder. Trial registration ID: JapicCTI-090980

AB - Background: S-288310, a cancer peptide vaccine composed of two HLA-A*24:02-restricted peptides derived from two oncoantigens, DEP domain-containing 1 (DEPDC1) and M-phase phosphoprotein 1 (MPHOSPH1), was investigated in urothelial carcinoma (UC) of the bladder. Patients and methods: Thirty eight HLA-A*24:02-positive patients with progressive UC were enrolled in this study. In the phase I part of the study, three patients each were treated with S-288310 at 1mg or 2 mg/peptide subcutaneously once a week to evaluate safety and tolerability. In the phase II, 32 patients were randomized to receive either 1mg or 2mg to evaluate the difference in cytotoxic T lymphocytes (CTL) induction and safety. Results: S-288310 was safe and well tolerated in the phase I. Of 27 patients evaluable for immune responses in the phase II, there was no difference in CTL induction rate between the 1mg (100%) and 2mg (80.0%) groups. Of 32 patients receiving S-288310 in the phase II, the most frequent drug-related AE was the injection site reaction that was observed in 29 patients (90.6%), but none of the patients discontinued administration due to these reactions and no dose relationship in the frequency and severity was observed. The objective response rate of the 32 patients was 6.3% and the disease control rate was 56.3%. The median overall survival (OS) rates for patients vaccinated with S-288310 after one regimen of chemotherapy, 2 regimens, or 3 or more were 14.4, 9.1 and 3.7 months, respectively, and 32.2% of patients post first-line treatment were alive at 2 years. OS of patients who showed CTL induction to both peptides was longer than that of those with CTL induction to no or one peptide. Conclusion: S-288310 was well-tolerated and effectively induced peptide-specific CTLs, which were correlated with longer survival for patients with UC of the bladder. Trial registration ID: JapicCTI-090980

UR - http://www.scopus.com/inward/record.url?scp=85019160407&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85019160407&partnerID=8YFLogxK

U2 - 10.1093/annonc/mdw675

DO - 10.1093/annonc/mdw675

M3 - Article

C2 - 27998971

AN - SCOPUS:85019160407

VL - 28

SP - 798

EP - 803

JO - Annals of Oncology

JF - Annals of Oncology

SN - 0923-7534

IS - 4

ER -