Gal Wald, MD, on the rationale for trial of BCG plus gemcitabine in NMIBC

In this video, Gal Wald, MD, shares the background and rationale for the study, “Initial Results Of A Phase II Trial Of Bacillus Calmette-Guérin (BCG) And Intravesical Gemcitabine For Patients With BCG-Exposed High-Grade Non-Muscle Invasive Bladder Cancer (NCT04179162),” which he presented at the Society of Urologic Oncology 25th Annual Meeting in Dallas, Texas. Wald is a fourth year urology resident at Weill Cornell Medicine in New York, New York.

Video Transcript:

These are preliminary results for a phase 2 multi-center trial for intravesical gemcitabine and BCG for BCG-exposed non–muscle-invasive bladder cancer. BCG-exposed patients represent a population with an unmet need. More than half of patients who initially respond to BCG monotherapy relapse within 5 years. These patients are typically given another course of BCG, but they tend to have even lower response rates. So, combination therapies have now become the forefront of our field, and we are trying to do better to avoid BCG-unresponsive disease, as well as progression to either muscle-invasive or metastatic disease. The current landscape of BCG and in combination with other therapies is quite heterogeneous. We have BCG with immune checkpoint blockade. However, that has an unacceptable toxicity profile for the majority of non–muscle-invasive bladder cancer patients. And it's quite expensive; it costs approximately a quarter million dollars per year per patient.

We have other recently FDA approved medications, BCG with IL-15 super agonist. That does not have single agent activity, and it's even more cost prohibitive. It's approximately half a million dollars per year per patient. So, intravesical chemo immunotherapy represents a whole other treatment paradigm for patients. Prior RCTs and meta-analyses have shown that combination therapy is more efficacious than BCG alone. But a lot of these trials have used mitomycin, which is a known vesicant and has significant urinary side effects.

When you compare gemcitabine to mitomycin, we've shown that in the BCG-exposed space, for example, it is more efficacious. It's also generally more tolerable with a favorable toxicity profile as it's not as strong of a vesicant. And it's less cost prohibitive. Not to mention that gemcitabine also has immunomodulatory effects. So, there's a biological rationale. It can reduce immunosuppressive cellular populations, including model derived suppressor cells, regulatory T-cells. It can prime the immune system. In preclinical animal models, we have shown that the combination of these 2 therapies is more efficacious than either therapy alone, which suggests either an additive or a synergistic effect. We've previously reported the final results of phase 1 showing that the combination of gemcitabine and BCG is very well tolerated. In that trial, there are no grade 3 to 5 adverse events.

This transcript was AI generated and edited by human editors for clarity.