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WASHINGTON -- Treatment with cretostimogene grenadenorepvec, an investigational intravesically delivered oncolytic immunotherapy, achieved high response rates in patients with high-risk non-muscle-invasive bladder cancer (NMIBC) unresponsive to Bacillus Calmette-Guérin (BCG), according to an interim analysis of the phase III BOND-003 trial.

Among 66 patients evaluable for efficacy, 75.7% (95% CI 63-85) achieved a complete response (CR) at any time, reported Mark Tyson, MD, MPH, of the Mayo Clinic in Scottsdale, Arizona, during a late-breaking abstract session at the Society of Urologic Oncology annual meeting.

The 3- and 6-month CR rates were 68.2% and 63.6%, respectively. These responses were durable over time, Tyson said, with 74.4% of responders maintaining their response for at least 6 months.

These results suggest that cretostimogene "has potential to disrupt the NMIBC treatment landscape," Tyson suggested.

"Recognizing that this is just an interim analysis, and also recognizing that comparing across studies is difficult because of underlying differences in the populations, [cretostimogene] would at least appear to compare favorably with the two current non-surgical standards of care," he noted.

Specifically, he pointed out that the CR rate with cretostimogene at any time, as well as the 6-month CR rate, stacked up well against the rates with nadofaragene firadenovec (Adstiladrin) and pembrolizumab (Keytruda).

He also noted that based on these interim results, the FDA granted a fast track designation to cretostimogene monotherapy in BCG-unresponsive carcinoma in situ with or without Ta/T1 papillary disease.

Cretostimogene grenadenorepvec works by replicating inside tumor cells, causing tumor cell lysis and immunogenic cell death. The rupture of the cancer cells then releases tumor-derived antigens and granulocyte macrophage colony-stimulating factor that can stimulate a systemic antitumor immune response.

The single-arm fully enrolled 116 patients from North America and the Asia-Pacific region. The 66 patients in this interim analysis were mostly men (76%) and white (56%), and had a median age of 73. Most (80%) had an Eastern Cooperative Oncology Group performance status score of 0 at baseline, and 18% had concomitant papillary disease. The cohort was heavily pretreated with a median of 14.4 prior BCG installations.

The dosing regimen included six weekly installations of cretostimogene, followed by maintenance therapy for responders, or repeat induction therapy for non-responders.

Of the patients who failed to respond to the first induction course of cretostimogene, 31% responded to the second induction course, including several patients who had a complete response beyond 9 months.

Out of 112 patients, 56.3% experienced a grade ≥1 treatment-related adverse event (TRAE), with no grade ≥3 TRAEs observed. The most common TRAEs were bladder spasm, pollakiuria, dysuria, micturition urgency, and hematuria.

Two patients had grade 2 serious TRAEs, but there were no treatment discontinuations due to adverse events or deaths reported.

Tyson said that the next phase of the BOND-003 study will include two amendments -- a treatment extension phase where complete responders are eligible for maintenance through year 3, and the addition of a BCG-unresponsive papillary cohort of 70 patients who will have the standard cretostimogene induction and maintenance schedule with the exception that there will not be repeat induction for non-responders.

Cretostimogene grenadenorepvec is also being evaluated in the phase II in combination with pembrolizumab for the same indication.

Additionally, Tyson noted that the phase III , with over 90 participating sites in North America, has been launched and will evaluate adjuvant cretostimogene versus transurethral resection of the bladder alone in intermediate-risk NMIBC.

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