A Phase 1/2 Single-arm Clinical Trial of Recombinant Bacillus Calmette-Guérin (BCG) VPM1002BC Immunotherapy in Non-muscle-invasive Bladder Cancer Recurrence After Conventional BCG Therapy: SAKK 06/14.

VPM1002BC is a genetically modified Mycobacterium bovis bacillus Calmette-Guérin (BCG) strain with potentially improved immunogenicity and attenuation.

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.

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.

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.

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.

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.

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.

We conducted a trial of VPM100BC, a genetically modified bacillus Calmette-Guérin (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.

European urology oncology. 2022 Jan 07 [Epub ahead of print]

Cyrill A Rentsch, George N Thalmann, Ilaria Lucca, Maciej Kwiatkowski, Grégory J Wirth, Räto T Strebel, Daniel Engeler, Augusto Pedrazzini, Clemens Hüttenbrink, Wolfgang Schultze-Seemann, Raimund Torpai, Lukas Bubendorf, Andreas Wicki, Beat Roth, Piet Bosshard, Heike Püschel, Daniel T Boll, Lukas Hefermehl, Florian Roghmann, Michael Gierth, Karin Ribi, Simon Schäfer, Stefanie Hayoz

Department of Urology, University Hospital Basel, University of Basel, Basel, Switzerland. Electronic address: ., Department of Urology, University Hospital Bern, University of Bern, Bern, Switzerland., Department of Urology, University Hospital Lausanne, Lausanne, Switzerland., Department of Urology, Cantonal Hospital Aarau, Aarau, Switzerland; Department of Urology, Academic Hospital Braunschweig, Braunschweig, Germany., Division of Urology, University Hospital Geneva, University of Geneva, Geneva, Switzerland., Department of Urology, Cantonal Hospital Chur, Chur, Switzerland., Department of Urology, Cantonal Hospital St. Gallen, St. Gallen, Switzerland., Department of Internal Medicine, Fondazione Oncologia Lago Maggiore, Locarno, Switzerland., Department of Urology, Nuremberg General Hospital, Paracelsus Medical University, Nuremberg, Germany., Department of Urology, University Hospital Freiburg im Breisgau., University of Freiburg im Bresigau, Freiburg im Breisgau, Germany., Department of Urology, Katholische Hospitalvereinigung Ostwestfalen gem. GmbH, Franziskus Hospital, Bielefeld, Germany., Institute of Medical Genetics and Pathology, University Hospital Basel, University of Basel, Basel, Switzerland., Department of Oncology, University Hospital, University of Basel, Basel, Switzerland., Department of Urology, University Hospital Basel, University of Basel, Basel, Switzerland., Department of Radiology and Nuclear Medicine, University Hospital Basel, University of Basel, Basel, Switzerland., Department of Urology, Cantonal Hospital Baden, Baden, Switzerland., Department of Urology, Marien Hospital, Ruhr-University Bochum, Herne, Germany., Department of Urology, University Hospital Regensburg, University of Regensburg, Regensburg, Germany., International Breast Cancer Study Group Coordinating Center, Bern, Switzerland; SAKK Coordinating Center, Bern, Switzerland., SAKK Coordinating Center, Bern, Switzerland.

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