Results of the phase I open label clinical trial SAKK 06/14 assessing safety of intravesical instillation of VPM1002BC, a recombinant mycobacterium Bacillus Calmette Guérin (BCG), in patients with non-muscle invasive bladder cancer and previous failure of conventional BCG therapy

Cyrill A Rentsch; Piet Bosshard; Grégoire Mayor; Malte Rieken; Heike Püschel; Grégory Wirth; Richard Cathomas; Gerald P Parzmair; Leander Grode; Bernd Eisele; Hitt Sharma; Manish Gupta; Sunil Gairola; Umesh Shaligram; Daniel Goldenberger; François Spertini; Régine Audran; Milica Enoiu; Simona Berardi; Stefanie Hayoz; Andreas Wicki

doi:10.1080/2162402X.2020.1748981

Results of the phase I open label clinical trial SAKK 06/14 assessing safety of intravesical instillation of VPM1002BC, a recombinant mycobacterium Bacillus Calmette Guérin (BCG), in patients with non-muscle invasive bladder cancer and previous failure of conventional BCG therapy

Oncoimmunology. 2020 Apr 21;9(1):1748981. doi: 10.1080/2162402X.2020.1748981. eCollection 2020.

Authors

Cyrill A Rentsch¹, Piet Bosshard^{1

2}, Grégoire Mayor³, Malte Rieken¹, Heike Püschel¹, Grégory Wirth³, Richard Cathomas⁴, Gerald P Parzmair⁵, Leander Grode⁵, Bernd Eisele⁵, Hitt Sharma⁶, Manish Gupta⁶, Sunil Gairola⁶, Umesh Shaligram⁶, Daniel Goldenberger⁷, François Spertini⁸, Régine Audran⁸, Milica Enoiu⁹, Simona Berardi⁹, Stefanie Hayoz⁹, Andreas Wicki¹⁰

Affiliations

¹ Department of Urology, University Hospital Basel, University of Basel, Basel, Switzerland.
² Department of Urology, University Hospital Bern, University of Bern, Bern, Switzerland.
³ Department of Urology, University Hospital Geneva, University of Geneva, Geneva, Switzerland.
⁴ Department of Oncology, Cantonal Hospital Chur, Chur, Switzerland.
⁵ Vakzine Projekt Management GmbH, Hannover, Germany.
⁶ Serum Institute of India Pvt. Ltd., Pune, India.
⁷ Department of Clinical Bacteriology & Mycology, University Hospital Basel, University of Basel, Basel, Switzerland.
⁸ Division of Immunology and Allergy, Lausanne University Hospital, Lausanne, Switzerland.
⁹ SAKK Coordinating Center, Bern, Switzerland.
¹⁰ Department of Oncology, University Hospital Basel, University of Basel, Switzerland.

Abstract

Background: VPM1002BC is a modified mycobacterium Bacillus Calmette Guérin (BCG) for the treatment of non-muscle invasive bladder cancer (NMIBC). The genetic modifications are expected to result in better immunogenicity and less side effects. We report on patient safety and immunology of the first intravesical application of VPM1002BC in human. Methods: Six patients with BCG failure received a treatment of 6 weekly instillations with VPM1002BC. Patients were monitored for adverse events (AE), excretion of VPM1002BC and cytokines, respectively. Results: No DLT (dose limiting toxicity) occurred during the DLT-period. No grade ≥3 AEs occurred. Excretion of VPM1002BC in the urine was limited to less than 24 hours. Plasma levels of TNFα significantly increased after treatment and blood-derived CD4+ T cells stimulated with PPD demonstrated significantly increased intracellular GM-CSF and IFN expression. Conclusion: The intravesical application of VPM1002BC is safe and well tolerated by patients and results in a potential Th1 weighted immune response.

Keywords: BCG-failure; GMO (genetically modified organism); NMIBC (Non-muscle-invasive bladder cancer); clinical trial; listeriolysin.

Publication types

Clinical Trial, Phase I
Research Support, Non-U.S. Gov't

MeSH terms

Administration, Intravesical
Aged
Aged, 80 and over
BCG Vaccine* / administration & dosage
Humans
Male
Mycobacterium bovis* / genetics
Mycobacterium bovis* / immunology
Urinary Bladder Neoplasms* / drug therapy

Substances

BCG Vaccine

Grants and funding

Serum Institute of India Pvt. Ltd., Pune, India. State Secretary for Education, Research and Innovation (SERI). Swiss Cancer Research Foundation (SCS). Swiss Cancer League (SCL).