Results of a phase I/II single arm clinical trial assessing efficacy, safety and tolerability of the recombinant Bacillus Calmette Guérin VPM1002BC in patients with non-muscle invasive bladder cancer recurrence after BCG induction with or without BCG maintenance therapy – SAKK 06/14

Abstract

VPM1002BC is a genetically modified Mycobacterium bovis Bacillus Calmette Guérin (BCG) strain with potentially improved immunogenicity and attenuation. Here, we report on efficacy, safety and tolerability of intravesical VPM1002BC for the treatment of non-muscle invasive bladder cancer (NMIBC). We designed a phase I/II single arm trial (NCT02371447). Patients were eligible with BCG failure (2008 EAU definition) and intermediate to high risk for NMIBC progression after conventional BCG therapy. The primary endpoint of the phase II part was defined as recurrence free survival (RFS) in the bladder 60 weeks after the first VPM1002BC instillation. From September 2015 to April 2018, a total of 40 patients (6 from phase I and 34 from phase II) were included into the trial. Patients were scheduled for a standard treatment of 6 weekly instillations with VPM1002BC followed by a maintenance regimen of 1 year. The study population consisted of 4 female and 36 male patients (median age 72 years). Previous maintenance BCG therapy was conducted in 14/40 patients. All recurrent tumours were high grade (2004 WHO definition) and 27 (67.5%) patients presented with carcinoma in situ (CIS). RFS in the bladder at 60 weeks after the first instillation was 49.3 % [95% CI 32.1%, 64.4%]. At the same time, progression in stage, grade or new occurrence of CIS had occurred in 12 (30%) patients, 3 of which had progression to muscle-invasive disease. Two patients died from bladder cancer (> 60 weeks after start of therapy). Over the whole course of therapy, treatment related grade 1, 2 and 3 AEs were observed in 15%, 52.5%, and 5% of the patients, respectively. No adverse events (AEs) grade ≥4 occurred. Two (5%) out of the 40 patients did not tolerate ≥ 5 instillations during induction. Fifteen patients (37.5%) received all scheduled instillations. One year after start of treatment, therapy with VPM100BC resulted in freedom from NMIBC recurrence in the bladder in almost half of the patients with recurrence after previous BCG exposure. The treatment is safe and well tolerated.