What You Should Know

  • Bladder cancer experts are closely watching PIVOT-006, a trial that could redefine treatment for patients with intermediate-risk non-muscle invasive disease.

    • Dr. Jorge Garcia, director of the GU Medical Oncology clinical and research programs at University Hospitals Seidman Cancer Center, views PIVOT-006 as a defining randomized trial that could determine whether cretostimogene becomes part of the standard of care — with the potential to increase complete responses, delay cystectomy, and prevent progression to muscle-invasive disease.

    • Dr. Leilei Xia, an Assistant Professor of Surgery at Penn Medicine, emphasizes the real-world impact for intermediate-risk NMIBC patients, noting the significant unmet need and the promise of adding an effective therapy after TURBT to meaningfully reduce recurrence.

Bladder cancer experts are eagerly awaiting what could be practice-changing: the results of the PIVOT-006 trial, a pivotal, randomized study comparing adjuvant intravesical cretostimogene grenadenorepvec (CG0070) versus surveillance, the current standard of care. In the trial, patients who have undergone transurethral resection of bladder tumor (TURBT) are randomized to receive adjuvant CG or observation. The goal is to determine whether this novel viral immunotherapy can safely and effectively reduce recurrence in a population at significant risk of progression.

“I think that’s absolutely the right study to be done because we have already single agent data looking at safety toxicity and efficacy with the CG compound, with this oncolytic immunotherapy,” says Dr. Jorge Garcia, director of the GU Medical Oncology clinical and research programs at University Hospitals Seidman Cancer Center. “In order for us to demonstrate that for those patients with high risk disease who are either unresponsive to therapy or who have high risk features that can actually develop into either CIS or go on to develop muscle invasive disease, the only way that we can demonstrate that the standard of care can be better is to actually use that compound.”

Proving It In A Randomized Study

Dr. Garcia explains that earlier single-agent data have already demonstrated encouraging safety and activity signals with CG. PIVOT-006 is designed to take the next critical step: proving in a randomized setting whether adding this therapy can meaningfully improve outcomes over standard management alone. For patients with intermediate-risk features as defined by AUA/SUO guidelines – who have had all visible disease removed via transurethral resection of bladder tumor (TURBT) — the stakes are substantial.

“The randomization is why I think this clinical trial is so important for the field. That trial will define and pave the way for whether or not CG is going to be the oncolytic immunotherapy that becomes part of the standard of care,” says Dr. Garcia. “At the end of the day, the more options we have for our patients, the better.”

The Endpoints That Matter

The primary endpoint of the study is recurrence-free survival (RFS). Dr. Garcia notes to other important goals of the trial including  RFS at 12 months and 24 months as well as the incidence of adverse events (AEs).

“We really want to preserve bladders,” Dr. Garcia notes. “And avoid or prevent perhaps the time to developing muscle invasive disease, which unequivocally changes the standard of care for you as a consumer, because then you will get systemic therapy plus your bladder resected or what we call bladder preservation, which is chemotherapy and radiation therapy, but with curative intent.”

A Significant Unmet Need in Intermediate-Risk NMIBC

Penn Medicine’s Dr. Leilei Xia, a medical oncologist and expert in the care of bladder cancer patients, emphasizes that this study could be quite important for intermediate risk NMIBC.

“This is potentially the first agent, if it gets approved, that we can use to decrease the chance of a recurrence for intermediate risk non invasive bladder cancer patients,” Dr. Xia says.”We are talking about a significant amount of patients that potentially can get additional therapy on top of the transurethral resection bladder tumor to decrease their chance of recurrence. I think it’s a huge benefit for those patients. As of right now, we don’t have anything.”

What Comes Next

Dr. Garcia emphasizes that even if the trial results confirm CG as the new standard of care for intermediate risk NMIBC patients, questions will still remain.

That includes “how you actually layer all these novel therapies that we’re developing, as you can imagine,” he says.