Perioperative chemo-immunotherapy has improved event-free survival (EFS) and overall survival (OS) in operable muscle-invasive bladder cancer (MIBC).¹ However, pathological complete response (pCR) rates remain below 40%, underscoring the need for more effective strategies.¹ Intravesical Bacillus Calmette-Guérin (BCG) has long been used to induce a local antitumor immune response in  on-muscle-invasive bladder cancer (NMIBC), and recombinant BCG (rBCG; VPM1002BC) has since been developed to enhance immunogenicity and safety through more rapid autophagy elimination.¹ Although rBCG has demonstrated promising efficacy and safety in NMIBC, its role in MIBC has been unclear.¹

At the 2026 ASCO Annual Meeting, Professor Richard Cathomas from the Swiss Cancer Institute presented the primary analysis of the phase 2 SAKK 06/19 study, demonstrating that the addition of intravesical rBCG to perioperative cisplatin/gemcitabine + atezolizumab is feasible and tolerable in operable MIBC.¹

SAKK 06/19 was a prospective, multicenter, single-arm, open-label phase 2 study that enrolled patients with cT2-T4a cN0/N1 urothelial carcinoma who had a World Health Organization (WHO) performance status of 0-1 and were eligible for cisplatin-based chemotherapy (glomerular filtration rate [GFR] >50mL/min).¹ Intravesical rBCG was administered once weekly for three doses starting on day 1, with atezolizumab every 3 weeks for four doses from day 1, and cisplatin/gemcitabine every 3 weeks for four cycles from day 22, followed by radical cystectomy with lymph node dissection (RC-LND).¹ Adjuvant atezolizumab was administered only to patients with residual ≥ypT2 or ypN+ disease following surgery.¹

A total of 47 patients were enrolled between April 2022 and April 2025, all of whom completed neoadjuvant treatment.¹ Patients were predominantly male, had good performance status, and presented mainly with localized, node-negative muscle-invasive urothelial carcinoma.¹ Of these, 40 patients underwent radical cystectomy and were evaluable for the primary endpoint.¹

The study met its primary endpoint, achieving a pCR at cystectomy rate of 68% (27/40), significantly exceeding the predefined efficacy threshold (one-sided 95% CI lower bound 53%; p<0.0001).¹ Overall, 83% achieved pCR (≤ypT1 ypN0), while 18% had residual ≥ypT2 disease and/or nodal involvement at surgery.¹ Preoperative clinical complete response (cCR) demonstrated a positive predictive value of 92% and a negative predictive value of 69%, supporting its potential role in identifying patients who may benefit from bladder preservation.¹ At a median follow-up of 16.7 months, estimated 12-month event-free survival (EFS) and overall survival (OS) rates were 90% and 96%, respectively.¹

The treatment regimen demonstrated a tolerable safety profile.¹ rBCG-related adverse events were predominantly grade 1/2, while grade 3/4 treatment-related adverse events (TRAEs) were primarily related to chemotherapy.¹ Importantly, no systemic BCG infections were reported.¹ The most common grade 3/4 TRAEs included neutropenia, thrombocytopenia, urinary tract infections, anemia, thromboembolic events, sepsis, and renal impairment.¹

A pre-planned propensity score-weighted comparison with the earlier SAKK 06/17 study further supported the potential contribution of rBCG.¹ Patients treated in SAKK 06/19 demonstrated significantly higher odds of achieving pCR compared with those receiving perioperative chemo-immunotherapy without rBCG (odds ratio=5.13; 95% CI: 2.63-10.02; p<0.001).¹

In conclusion, the primary analysis of the phase 2 SAKK 06/19 study demonstrated that adding intravesical rBCG to perioperative cisplatin/gemcitabine + atezolizumab achieved high pCR and pathological overall response (PaR) with a feasible and tolerable safety profile in patients with operable MIBC.¹ While these findings warrant validation in randomized trials, they provide preliminary evidence supporting the potential role of intravesical rBCG in augmenting perioperative chemo-immunotherapy for MIBC.¹