Gary Steinberg, MD, on next steps for clinical development of bel-sar in NMIBC

In this video, Gary D. Steinberg, MD, discusses remaining questions on bel-sar, a virus-drug conjugate (VDC) currently in phase 1 development for non–muscle-invasive bladder cancer (NMIBC). Steinberg is a professor of urology at Rush University Medical Center in Chicago, Illinois.

Video Transcript:

I think that there's a couple of things. Number 1 is I think that we have to nail down the dose. I think that we've been using a relatively low dose. As we know, these VDCs can be used in other cancers. They've been very effectively used in choroidal uveal melanoma with be-sar. So, we really have to nail down the dosage. I would suspect that larger papillary, non-invasive tumors would potentially require a larger dose. We also have to assess: can we do it all at one time? Can we do the VDC intravesical installation and then light activate the same day? How much time do you have to wait? Is there a benefit to waiting 24 hours? 48 hours? More importantly, can we re-dose? Would it be more effective, especially if we have a larger papillary tumor, to dose multiple times? Once a week? Once every other week? Would we see even more immunologic infiltrate if we waited 3 to 4 weeks after the treatment? Would we see more complete resolution of the tumors visually just by waiting longer and letting the immune system work longer? There are a number of different things that we need to iron out.

But more importantly, I think that we need to identify a patient population, most likely the intermediate risk, non–muscle-invasive bladder cancer patients that have low-grade disease. Ideally, I'd like to see us also treat some patients with papillary Ta high grade disease. With the mechanism of action the way it is, there's no reason to think that there would be any difference between results with low-grade vs high-grade. High-grade may need a larger dose, more treatments, or more time to allow the immune system to see efficacy.

I think that most importantly, we need to continue to make sure that it's safe and that there are no untoward adverse events or immune-related adverse events [and] that it is a local treatment. It does not cause systemic toxicity. I think that we need to nail down the treatment algorithm. How much of the dose? How many injections? When we talk about bladder cancer, non-muscle-invasive bladder cancer, we talk about an individual tumor, but as we know, many times there's a field change effect within the bladder. Even though we only may see 1 tumor, there may be a number of smaller tumors throughout the bladder that we can't visually see. We know that the cells may all have cancer, but just set in a different time clock. The other thing that we believe will be important to see is it not only effective where we inject a tumor and turn the light on in the tumor, but will there be abscopal effects throughout the bladder? In other words, tumors that are not where we injected, but say 2 or 3 centimeters away, are they being affected? Can we treat those tumors as well? And I suspect that we will, but we probably need a longer interval from treatment to resection to allow the immune system to work throughout the bladder. Those are other things that that we have to investigate. How much to treat? How often? Can you re-treat? How much time can we give to allow the VDCs in the immune system to work?

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