PMID- 35012889
OWN - NLM
STAT- MEDLINE
DCOM- 20220512
LR  - 20220531
IS  - 2588-9311 (Electronic)
IS  - 2588-9311 (Linking)
VI  - 5
IP  - 2
DP  - 2022 Apr
TI  - A Phase 1/2 Single-arm Clinical Trial of Recombinant Bacillus Calmette-Guerin 
      (BCG) VPM1002BC Immunotherapy in Non-muscle-invasive Bladder Cancer Recurrence 
      After Conventional BCG Therapy: SAKK 06/14.
PG  - 195-202
LID - S2588-9311(21)00222-4 [pii]
LID - 10.1016/j.euo.2021.12.006 [doi]
AB  - BACKGROUND: VPM1002BC is a genetically modified Mycobacterium bovis bacillus 
      Calmette-Guerin (BCG) strain with potentially improved immunogenicity and 
      attenuation. OBJECTIVE: To report on the efficacy, safety, tolerability and 
      quality of life of intravesical VPM1002BC for the treatment of 
      non-muscle-invasive bladder cancer (NMIBC) recurrence after conventional BCG 
      therapy. DESIGN, SETTING, AND PARTICIPANTS: We designed a phase 1/2 single-arm 
      trial (NCT02371447). Patients with recurrent NMIBC after BCG induction +/- BCG 
      maintenance therapy and intermediate to high risk for cancer progression were 
      eligible. INTERVENTION: Patients were scheduled for standard treatment of six 
      weekly instillations with VPM1002BC followed by maintenance for 1 yr. Treatment 
      was stopped in cases of recurrence. OUTCOME MEASUREMENTS AND STATISTICAL 
      ANALYSIS: The primary endpoint was defined as the recurrence-free rate (RFR) in 
      the bladder 60 wk after trial registration. The sample size was calculated based 
      on the assumption that >/=30% of the patients would be without recurrence at 60 wk 
      after registration. RESULTS AND LIMITATIONS: After exclusion of two ineligible 
      patients, 40 patients remained in the full analysis set. All treated tumours were 
      of high grade and 27 patients (67.5%) presented with carcinoma in situ. The 
      recurrence-free rate in the bladder at 60 wk after trial registration was 49.3% 
      (95% confidence interval [CI] 32.1-64.4%) and remained at 47.4% (95% CI 
      30.4-62.6%] at 2 yr and 43.7% (95% CI 26.9-59.4%) at 3 yr after trial 
      registration. At the same time, progression to muscle-invasive disease had 
      occurred in three patients and metastatic disease in four patients. 
      Treatment-related grade 1, 2, and 3 adverse events (AEs) were observed in 14.3%, 
      54.8%, and 4.8% of the patients, respectively. No grade >/=4 AEs occurred. Two of 
      the 42 patients did not tolerate five or more instillations during induction. 
      Limitations include the single-arm trial design and the low number of patients 
      for subgroup analysis. CONCLUSIONS: At 1 yr after treatment start, almost half of 
      the patients remained recurrence-free after therapy with VPM100BC. The primary 
      endpoint of the study was met and the therapy is safe and well tolerated. PATIENT 
      SUMMARY: We conducted a trial of VPM100BC, a genetically modified bacillus 
      Calmette-Guerin (BCG) strain for treatment of bladder cancer not invading the 
      bladder muscle. At 1 year after the start of treatment, almost half of the 
      patients with a recurrence after previous conventional BCG were free from 
      non-muscle-invasive bladder cancer (NMIBC). The results are encouraging and 
      VPM1002BC merits further evaluation in randomised studies for patients with 
      NMIBC.
CI  - Copyright (c) 2021 European Association of Urology. Published by Elsevier B.V. All 
      rights reserved.
FAU - Rentsch, Cyrill A
AU  - Rentsch CA
AD  - Department of Urology, University Hospital Basel, University of Basel, Basel, 
      Switzerland. Electronic address: cyrill.rentsch@usb.ch.
FAU - Thalmann, George N
AU  - Thalmann GN
AD  - Department of Urology, University Hospital Bern, University of Bern, Bern, 
      Switzerland.
FAU - Lucca, Ilaria
AU  - Lucca I
AD  - Department of Urology, University Hospital Lausanne, Lausanne, Switzerland.
FAU - Kwiatkowski, Maciej
AU  - Kwiatkowski M
AD  - Department of Urology, Cantonal Hospital Aarau, Aarau, Switzerland; Department of 
      Urology, Academic Hospital Braunschweig, Braunschweig, Germany.
FAU - Wirth, Gregory J
AU  - Wirth GJ
AD  - Division of Urology, University Hospital Geneva, University of Geneva, Geneva, 
      Switzerland.
FAU - Strebel, Rato T
AU  - Strebel RT
AD  - Department of Urology, Cantonal Hospital Chur, Chur, Switzerland.
FAU - Engeler, Daniel
AU  - Engeler D
AD  - Department of Urology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland.
FAU - Pedrazzini, Augusto
AU  - Pedrazzini A
AD  - Department of Internal Medicine, Fondazione Oncologia Lago Maggiore, Locarno, 
      Switzerland.
FAU - Huttenbrink, Clemens
AU  - Huttenbrink C
AD  - Department of Urology, Nuremberg General Hospital, Paracelsus Medical University, 
      Nuremberg, Germany.
FAU - Schultze-Seemann, Wolfgang
AU  - Schultze-Seemann W
AD  - Department of Urology, University Hospital Freiburg im Breisgau., University of 
      Freiburg im Bresigau, Freiburg im Breisgau, Germany.
FAU - Torpai, Raimund
AU  - Torpai R
AD  - Department of Urology, Katholische Hospitalvereinigung Ostwestfalen gem. GmbH, 
      Franziskus Hospital, Bielefeld, Germany.
FAU - Bubendorf, Lukas
AU  - Bubendorf L
AD  - Institute of Medical Genetics and Pathology, University Hospital Basel, 
      University of Basel, Basel, Switzerland.
FAU - Wicki, Andreas
AU  - Wicki A
AD  - Department of Oncology, University Hospital, University of Basel, Basel, 
      Switzerland.
FAU - Roth, Beat
AU  - Roth B
AD  - Department of Urology, University Hospital Bern, University of Bern, Bern, 
      Switzerland.
FAU - Bosshard, Piet
AU  - Bosshard P
AD  - Department of Urology, University Hospital Basel, University of Basel, Basel, 
      Switzerland.
FAU - Puschel, Heike
AU  - Puschel H
AD  - Department of Urology, University Hospital Basel, University of Basel, Basel, 
      Switzerland.
FAU - Boll, Daniel T
AU  - Boll DT
AD  - Department of Radiology and Nuclear Medicine, University Hospital Basel, 
      University of Basel, Basel, Switzerland.
FAU - Hefermehl, Lukas
AU  - Hefermehl L
AD  - Department of Urology, Cantonal Hospital Baden, Baden, Switzerland.
FAU - Roghmann, Florian
AU  - Roghmann F
AD  - Department of Urology, Marien Hospital, Ruhr-University Bochum, Herne, Germany.
FAU - Gierth, Michael
AU  - Gierth M
AD  - Department of Urology, University Hospital Regensburg, University of Regensburg, 
      Regensburg, Germany.
FAU - Ribi, Karin
AU  - Ribi K
AD  - International Breast Cancer Study Group Coordinating Center, Bern, Switzerland; 
      SAKK Coordinating Center, Bern, Switzerland.
FAU - Schafer, Simon
AU  - Schafer S
AD  - SAKK Coordinating Center, Bern, Switzerland.
FAU - Hayoz, Stefanie
AU  - Hayoz S
AD  - SAKK Coordinating Center, Bern, Switzerland.
LA  - eng
SI  - ClinicalTrials.gov/NCT02371447
PT  - Clinical Trial, Phase I
PT  - Clinical Trial, Phase II
PT  - Journal Article
DEP - 20220107
PL  - Netherlands
TA  - Eur Urol Oncol
JT  - European urology oncology
JID - 101724904
RN  - 0 (BCG Vaccine)
SB  - IM
MH  - Administration, Intravesical
MH  - BCG Vaccine/therapeutic use
MH  - Female
MH  - Humans
MH  - Immunotherapy
MH  - Male
MH  - *Mycobacterium bovis
MH  - Quality of Life
MH  - *Urinary Bladder Neoplasms/drug therapy/pathology
OTO - NOTNLM
OT  - Bacillus Calmette-Guerin
OT  - Genomically modified organism
OT  - Non-muscle-invasive bladder cancer
OT  - Phase 2 single-arm trial
OT  - VPM1002BC
EDAT- 2022/01/12 06:00
MHDA- 2022/05/14 06:00
CRDT- 2022/01/11 06:08
PHST- 2021/07/06 00:00 [received]
PHST- 2021/10/27 00:00 [revised]
PHST- 2021/12/15 00:00 [accepted]
PHST- 2022/01/12 06:00 [pubmed]
PHST- 2022/05/14 06:00 [medline]
PHST- 2022/01/11 06:08 [entrez]
AID - S2588-9311(21)00222-4 [pii]
AID - 10.1016/j.euo.2021.12.006 [doi]
PST - ppublish
SO  - Eur Urol Oncol. 2022 Apr;5(2):195-202. doi: 10.1016/j.euo.2021.12.006. Epub 2022 
      Jan 7.