Cretostimogene for Bladder Cancer: BOND-003 Study Ramifications

Mark D. Tyson, MD, of Mayo Clinic, discusses the role of cretostimogene grenadenorepvec in treating BCG-unresponsive NMIBC, with a focus on Cohort P of the BOND-003 trial. Dr. Tyson examines the comprehensive event-free survival outcomes, the streamlined administration process compared to earlier trials, and how the ongoing PIVOT-006 and CORE-008 trials are refining the use of cretostimogene grenadenorepvec.

Transcript

With all-cause event-free survival as the primary outcome of the BOND-003 study, what specific benchmarks are you looking to achieve, and how do you envision these results influencing the current treatment paradigm for bladder cancer?

Dr. Tyson: With respect to the event-free survival piece, that is going to include all high-grade recurrences, progression events, cystectomy events, deaths, metastatic disease. It’s essentially a composite outcome that includes all of these different possibilities that could happen to a patient.

And so, in terms of how I envision these results influencing the current paradigm, well, I think if there’s a similar, excellent response rate in Cohort P as we’ve observed in Cohort P, yes, we won’t know the counterfactual outcome, so we won’t know the average treatment effects, but we’ll have fairly good insight into efficacy. I think if we still see a pretty good response rate with the good durability that we’ve seen in Cohort C. And I think should cretostimogene imaging become commercially available, I think it would be an option for patients to choose, even if they don’t have CIS potentially based upon what Cohort P shows. So, that’s the outcome, and I think that’s potentially how it could influence the current treatment paradigm.

If the results of BOND-003 Cohort P prove successful, what are the next steps for cretostimogene in terms of broader clinical application, regulatory approvals, and integration into bladder-sparing strategies for high-risk patients?

Dr. Tyson: This is where I give CG a lot of credit. They have a very cogent plan here in terms of how they’re generating data. So, I don’t think that the plan for development of cretostimogene depends on the success of Cohort P. They’ve already achieved a fair amount of success with Cohort C, and then they have PIVOT 6, which is a randomized phase 3, comparing cretostimogene to observation in patients with intermediate risks. So from that trial, they’re going to know average treatment effects of cretostimogene, and that’s going to be a really important data point for those of us who are following this space.

And then I think from there, they have a CORE-8 trial where they’re looking at refining how the drug is given. The LEGACY trials, the drug was actually a little difficult to give. There was a five-step process where you were given DDM and saline, and the whole process took a long time and it was not ideal. But in Cohort P and in PIVOT-6, there’s a two-step process and it’s a lot easier, a lot more streamlined. Cohort 8 is testing both of those. There’s a BCG-naïve cohort where they’re randomizing patients to each of those two, so that’ll be an important developmental piece as well. And then, Cohort 8 is also studying BCG-exposed.

So you can see they’re generating a lot of data in this space to answer important questions that I think as a whole, really doesn’t depend on whether Cohort P is successful or not. But certainly if Cohort P is successful, then it would, I think, lend some evidence to those of us that are treating a lot of patients in this space for potential use in BCG-unresponsive, papillary-only patients.