PMID- 38060587
OWN - NLM
STAT- MEDLINE
DCOM- 20240403
LR  - 20240404
IS  - 1538-8514 (Electronic)
IS  - 1535-7163 (Print)
IS  - 1535-7163 (Linking)
VI  - 23
IP  - 4
DP  - 2024 Apr 2
TI  - TAS0313 plus Pembrolizumab for Post-Chemotherapy Immune Checkpoint 
      Inhibitor-Naive Locally Advanced or Metastatic Urothelial Carcinoma.
PG  - 532-540
LID - 10.1158/1535-7163.MCT-23-0187 [doi]
AB  - We evaluated the efficacy and safety of TAS0313, a multi-epitope long peptide 
      vaccine, plus pembrolizumab in post-chemotherapy immune checkpoint 
      inhibitor-naive patients with locally advanced/metastatic urothelial carcinoma 
      (la/mUC). TAS0313 9 mg was administered subcutaneously followed by pembrolizumab 
      200 mg on Day 1, and as monotherapy on Day 8 and 15 of Cycles 1 and 2, and Day 1 
      of subsequent cycles in 21-day cycles. The primary endpoint was the objective 
      response rate (ORR). Secondary endpoints included progression-free survival 
      (PFS), overall survival (OS), and safety. Biomarkers of response were assessed. 
      In 36 patients enrolled, the ORR was 33.3% (complete response: 7 patients; 
      partial response: 5 patients). Median PFS was 5.0 months; 6- and 12-month 
      progression-free rates were 46.4% and 36.5%, respectively. Median OS was not 
      reached; 6-, 12-, and 24-month OS rates were 83.3%, 72.2%, and 55.1%, 
      respectively. In post hoc analysis, patients with a tumor infiltrating CD8+ 
      lymphocyte (CD8+ TIL) count >/=99 and/or programmed cell death ligand 1 (PD-L1) 
      combined positive score (CPS) >/=50 and lymphocyte count >1,380 cells/muL had higher 
      ORRs and prolonged PFS versus patients with a CD8+ TIL count <99, PD-L1 CPS <50, 
      and lymphocyte count </=1,380 cells/muL. Thirty-four (94.4%) patients receiving 
      combination therapy experienced treatment-related adverse events (AE), with 
      pyrexia (n = 15, 41.7%), injection-site reactions (n = 15, 41.7%), injection-site 
      induration (n = 6, 16.7%), and malaise (n = 6, 16.7%) the most common. No grade 
      >/=3 treatment-related AEs occurred in >/=10% of patients. TAS0313 plus pembrolizumab 
      combination therapy showed promising efficacy and manageable safety in la/mUC. 
      Clinical Trial Registration: JapicCTI-183824.
CI  - (c)2023 The Authors; Published by the American Association for Cancer Research.
FAU - Nishiyama, Hiroyuki
AU  - Nishiyama H
AUID- ORCID: 0000-0001-7423-596X
AD  - Department of Urology, University of Tsukuba, Tsukuba, Japan.
FAU - Yonese, Junji
AU  - Yonese J
AUID- ORCID: 0000-0001-9266-4020
AD  - Department of Urology, Cancer Institute Hospital of Japanese Foundation for 
      Cancer Research, Tokyo, Japan.
FAU - Kawahara, Takashi
AU  - Kawahara T
AUID- ORCID: 0000-0001-6494-819X
AD  - Department of Urology, University of Tsukuba, Tsukuba, Japan.
FAU - Matsumoto, Ryuji
AU  - Matsumoto R
AUID- ORCID: 0000-0001-9363-9054
AD  - Department of Renal and Genitourinary Surgery, Hokkaido University, Sapporo, 
      Japan.
FAU - Miyake, Hideaki
AU  - Miyake H
AUID- ORCID: 0000-0003-0563-4160
AD  - Department of Urology, Hamamatsu University School of Medicine, Hamamatsu, Japan.
FAU - Matsubara, Nobuaki
AU  - Matsubara N
AUID- ORCID: 0000-0002-9203-4245
AD  - Division of Medical Oncology, National Cancer Center Hospital East, Chiba, Japan.
FAU - Uemura, Hiroji
AU  - Uemura H
AUID- ORCID: 0000-0001-7943-1564
AD  - Department of Urology and Renal Transplantation, Yokohama City University Medical 
      Center, Yokohama, Japan.
FAU - Eto, Masatoshi
AU  - Eto M
AUID- ORCID: 0000-0002-3312-9930
AD  - Department of Urology, Kyushu University Graduate School of Medical Sciences, 
      Fukuoka, Japan.
FAU - Azuma, Haruhito
AU  - Azuma H
AUID- ORCID: 0000-0001-5497-1679
AD  - Department of Urology, Osaka Medical and Pharmaceutical University, Takatsuki, 
      Japan.
FAU - Obara, Wataru
AU  - Obara W
AUID- ORCID: 0000-0003-2720-9640
AD  - Department of Urology, Iwate Medical University, Yahaba, Japan.
FAU - Terai, Akito
AU  - Terai A
AUID- ORCID: 0009-0008-1121-6188
AD  - Department of Urology, Kurashiki Central Hospital, Kurashiki, Japan.
FAU - Fukasawa, Satoshi
AU  - Fukasawa S
AUID- ORCID: 0000-0002-4759-4999
AD  - Prostate Center and Division of Urology, Chiba Cancer Center, Chiba, Japan.
FAU - Suekane, Shigetaka
AU  - Suekane S
AUID- ORCID: 0000-0003-1150-2893
AD  - Department of Urology, Kurume University School of Medicine, Kurume, Japan.
LA  - eng
GR  - n/a/
PT  - Journal Article
PL  - United States
TA  - Mol Cancer Ther
JT  - Molecular cancer therapeutics
JID - 101132535
RN  - DPT0O3T46P (pembrolizumab)
RN  - 0 (Immune Checkpoint Inhibitors)
RN  - 0 (B7-H1 Antigen)
RN  - 0 (Antineoplastic Agents, Immunological)
RN  - 0 (Antibodies, Monoclonal, Humanized)
SB  - IM
MH  - Humans
MH  - Immune Checkpoint Inhibitors/therapeutic use
MH  - *Carcinoma, Transitional Cell/drug therapy
MH  - B7-H1 Antigen/metabolism
MH  - *Antineoplastic Agents, Immunological/adverse effects
MH  - *Urinary Bladder Neoplasms/drug therapy/etiology
MH  - Antineoplastic Combined Chemotherapy Protocols/adverse effects
MH  - *Antibodies, Monoclonal, Humanized
PMC - PMC10985476
EDAT- 2023/12/07 18:42
MHDA- 2024/04/03 06:44
PMCR- 2024/04/02
CRDT- 2023/12/07 13:52
PHST- 2023/03/31 00:00 [received]
PHST- 2023/08/18 00:00 [revised]
PHST- 2023/12/01 00:00 [accepted]
PHST- 2024/04/03 06:44 [medline]
PHST- 2023/12/07 18:42 [pubmed]
PHST- 2023/12/07 13:52 [entrez]
PHST- 2024/04/02 00:00 [pmc-release]
AID - 731542 [pii]
AID - MCT-23-0187 [pii]
AID - 10.1158/1535-7163.MCT-23-0187 [doi]
PST - ppublish
SO  - Mol Cancer Ther. 2024 Apr 2;23(4):532-540. doi: 10.1158/1535-7163.MCT-23-0187.