Robert Svatek, MD, discusses the design of the PIVOT-006 trial

In this interview, Robert Svatek, MD, highlights the design of the phase 3 PIVOT-006 trial, which is evaluating cretostimogene grenadenorepvec vs surveillance in the treatment of patients with intermediate-risk non-muscle invasive bladder cancer. Svatek is a professor of medicine at UT Health San Antonio.

Video Transcript:

Could you describe the background/rationale for this trial?

Let's start with the population that we're targeting. This is the intermediate-risk, non–muscle-invasive bladder population. What does that mean? These are patients that have non-muscle-invasive bladder cancer that mainly stages TA. There is some patients with T1 that would be applicable, but it's largely patients with superficial stage A bladder cancer. Most of them have low-grade disease. Those that have high-grade would be small tumors, solitary. So, this is a very unique population. They have a higher risk of recurrence and progression than the low-grade, but lower risk of recurrence progression than high-grade. So, that's the target population. The trial is meant to define or test this agent in this population for which currently there's not an established standard of care. If you look out in the community about what's being done for patients with this intermediate-risk, it's very diverse. The guidelines reflect the absence of any consensus on how to best treat these patients.

How is the study designed? What are the key end points?

First of all, this is a randomized controlled trial. Patients are randomized in a 1:1 fashion to either cretostimogene vs standard of care, so observation. This is open-label, so patients are not blinded, physicians are not blinded. The cretostimogene arm is given a total of 18 installations, so creto over 1 year. That includes an induction course, which is once a week for 6 weeks, and then maintenance regimen. If the patients are responding, meaning they're not having tumor relapse, they'll go on to receive maintenance, which occurs at months 3, 6, 9, and 12. The maintenance is once a week for 3 weeks at month 3 and month 6, and then once a week, just 1 installation at month 9 and month 12. That's a total of 18 installations over a year's period. The observation arm is patients are observed with surveillance, meaning they undergo cystoscopy, just like you would in normal practice.

The primary end point is recurrence-free survival. The study hopes to enroll roughly up to 430 patients. It could be less than that. If the interim assessment shows that there's a big difference between the2 arms, they may enroll less. But it's up to 430 [patients,] and the enrollment is expected to occur within 36 months. [It] may be much sooner, but within 36 months. There are other secondary objectives, like recurrence at 1 year, recurrence at 2 years, progression, some exploratory objectives, looking at biologic activity, E2F promoter, for example, and urine markers and things like that. But the primary end point is recurrence-free survival.

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