Phase 1/2 trial evaluates recombinant BCG in BCG-naïve NMIBC

A phase 1/2 trial evaluating recombinant Mycobacterium BCG in BCG-naïve patients with non-muscle-invasive bladder cancer has begun activating U.S. clinical sites, offering a potential path toward expanding the supply of effective intravesical immunotherapy in a disease where conventional BCG shortages have created a persistent unmet need.

In this video, recorded at the 2026 American Urological Association Annual Meeting in Washington, DC, Joshua J. Meeks, MD, PhD, provides an overview of the trial.

The ResQ133A-NMIBC trial (NCT06800963), sponsored by ImmunityBio, Inc, is enrolling up to 50 patients with high-risk NMIBC—including carcinoma in situ, papillary disease, or both—who have not previously received BCG. Eligible patients must have no residual disease after TURBT and an ECOG performance status of 2 or less. The treatment protocol mirrors standard BCG practice: six weekly intravesical instillations during induction, followed by maintenance therapy per AUA guidelines for up to three years in patients who respond. Response assessments occur every 12 weeks through week 52, evaluated by cystoscopy, confirmatory biopsy, and urine cytology.

"The major challenge here is that we just don't have enough BCG in the US," said Meeks, the Edward M. Schaeffer, MD, PhD Professor of Urology and associate professor of urology, biochemistry, and molecular genetics at Northwestern University Feinberg School of Medicine in Chicago, Illinois. "The broadest part of the pyramid of patients with bladder cancer is BCG-naïve—that's the biggest population that actually needs more BCG."

The primary objective is safety and tolerability; secondary end points include complete response rate and duration in patients with CIS, and disease-free survival in papillary Ta and T1 disease. Meeks characterized the trial as largely observational in its orientation.

"It's not a dose-finding study because the dose is already set," he said. "It's really more about looking at the US population"—the FDA has requested US-specific data to complement an expanded access program in which more than 700 patients have already been treated with rBCG globally.

The scientific rationale for the recombinant modification centers on the mechanism by which Mycobacterium tuberculosis evades immune clearance. In conventional BCG, the urease C gene enables the bacterium to survive inside the phagosome by modulating pH—effectively blunting immune recognition. In rBCG, the urease C locus is replaced by the listeriolysin gene from Listeria. This substitution disrupts the pH-buffering mechanism, promotes phagosomal breakdown, and enhances antigen presentation—increasing immunogenicity against the mycobacterial antigens.

"That's the mechanism of how it works and how it's designed," Meeks said.

Prior European data from the SAKK06/14 trial—conducted in BCG-unresponsive patients, a more refractory population than the BCG-naïve cohort in ResQ133A-NMIBC—demonstrated a 50% response rate at 12 months with no dose-limiting toxicities and no grade 3 adverse events. Meeks noted that the tolerability profile observed in that trial supports the expectation of similar safety in the current study, though the patient population is meaningfully different.

Meeks positioned the trial explicitly within the landscape of emerging NMIBC therapies. Unlike agents such as N-803 (Anktiva), which requires BCG and is therefore applicable only to the BCG-unresponsive segment—approximately 15% to 20% of NMIBC patients—rBCG targets the BCG-naïve majority.