ResQ133A-NMIBC: A phase 1/2 clinical trial of intravesical recombinant mycobacterium bacillus Calmette-Guerin (rBCG) in participants living with non-muscle invasive bladder cancer eligible to receive conventional BCG.

TPS884 Background: Intravesical Bacillus Calmette-Guerin (BCG) is a standard and widely used therapy for non-muscle invasive bladder cancer (NMIBC). However, the global shortage of BCG has presented a need for alternative sources of BCG and/or treatments. Recombinant mycobacterium BCG (rBCG) may offer an alternative to BCG for both induction and maintenance therapy in NMIBC. Two gene modifications have been implemented in rBCG to improve its immunogenicity and safety in comparison to earlier strains and formulations of BCG. The urease G gene is deleted and the listeriolysin gene is added in this strain specifically designed for bladder cancer therapy. rBCG has completed Phase 1/2 human clinical studies in Europe as an immunotherapy in patients with NMIBC. As reported in the SAKK06/14 trial, rBCG VPM1002BC was found to be efficacious and safe in NMIBC recurrence after conventional BCG therapy [Rentsch 2022 ]. In ResQ133A-NMIBC, the safety and preliminary efficacy of rBCG will be assessed in NMIBC participants who have not received BCG (BCG-naïve). Methods: ResQ133A-NMIBC study is a phase 1/2, open-label, multicenter trial evaluating intravesical rBCG in BCG-naïve participants with NMIBC. To be eligible, participants must be 18 years or older, have histologically confirmed NMIBC, and be absent from resectable disease after TURBT procedures. They must also have an ECOG performance status of < 3. Exclusion criteria include participants with a life expectancy of less than 2 years, certain laboratory abnormalities, previous BCG treatment, or muscle-invasive bladder cancer are excluded from the study. Additionally, individuals with other progressing cancers within the past 5 years or being treated with investigational therapy are also not eligible. The study treatment involves weekly intravesical instillation of 1–19.2e8 CFU (1 vial) of rBCG for 6 weeks during the induction phase. For participants benefiting from treatment, maintenance installations will be administered weekly for 3 weeks, every 3 months. Response assessments occur every 12 weeks (3 months) through week 52 (month 12). Responses will be assessed by cystoscopy, confirmatory bladder biopsy, and urine cytology. The primary objective of the study is to assess the safety of intravesical rBCG, including vital signs, clinically significant changes in safety laboratory tests, and the incidence and severity of adverse events (AEs). The secondary objectives are to determine the complete response (CR) rate and median duration of CR in bladder CIS +/- Ta/T1 papillary, as well as disease-free survival in primary or recurrent papillary Ta and/or T1 disease. Response assessments will occur every 12 weeks through week 52. As of October 21, 2025, the study is open and awaiting the enrollment of its first participant. Clinical trial information: NCT06800963 .