Key Findings From BOND-003: Cretostimogene Grenadenorepvec in NMIBC

Opinion
Video

Mark D. Tyson, II, MD, MPH, discusses the safety and efficacy findings from the BOND-003 trial of cretostimogene grenadenorepvec in high-risk Bacillus Calmette-Guérin-unresponsive non-muscle-invasive bladder cancer with carcinoma in situ.

Mark D. Tyson, II, MD, MPH, a urologic oncologist at Mayo Clinic in Phoenix, Arizona, discusses the safety and efficacy findings from the BOND-003 trial (NCT04452591) of cretostimogene grenadenorepvec for the treatment of patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), which were presented at the 2024 American Urological Association (AUA) Annual Meeting.

The single-arm, open-label BOND-003 study was developed to assess and confirm the clinical activity of cretostimogene grenadenorepvec in this patient population. A total of 112 patients with high-risk BCG-unresponsive NMIBC were enrolled.

Results from the phase 3 BOND-003 study demonstrated sustained, durable complete responses (CR) over 12 months with cretostimogene grenadenorepvec, a novel investigational oncolytic immunotherapy. Notably, the CR rate in this patient population was 75.2%.

Looking at safety, no grade 3 or higher treatment-related adverse events (TRAEs) or deaths were reported. Two patients (1.8%) had serious TRAEs (Grade 2). There was also no treatment-related discontinuation of cretostimogene seen.

A total of 94.5% of patients completed all expected treatments, and TRAEs were observed in 70 patients (62.5%). As of the safety cutoff date of January 31, 2024, the most frequently observed TRAEs (≥10%) consisted of bladder spasm, pollakiuria, dysuria, micturition urgency, and hematuria.

Transcription:

0:09 | In total, 112 patients enrolled in BOND-003, and the data presented here are up to a cutoff date of April 1, 2024. In terms of baseline characteristics, most patients were White, male, and Medicare age. Eighteen percent of patients did have concomitant papillary disease, and as expected, the cohort was heavily pretreated with the median number of prior BCG installations of 12, with several other patients also having received pembrolizumab [Keytruda].

0:41 | In terms of the efficacy analysis, the complete response rate at any time point for all patients based upon central path review was 75.2%, with the confidence interval indicating a range of plausible CRs between 65% and 83%. The swimmers plot is shown here, and the key observation worth noting is that 54% of patients who did not respond to the initial induction course of cretostimogene responded to the second induction course of cretostimogene with several patients whose response was durable to beyond 12 months. This speaks to the oncolytic immunotherapeutic mechanism of action, whereby the immune system switches from innate to adaptive, as seen with the second induction course of BCG.

1:30 | Secondly, of the 35 patients who hit the 12-month time point, 29 or 83% have maintained a duration of response of greater than 12 months with 22 complete responders still pending. Lastly, 92% of patients had not required a cystectomy at the 1-year time point.

1:52 | In terms of tolerability, cretostimogene has generally been well-tolerated. There were no great 3 treatment-related adverse events and no deaths. There were 2 grade 2 serious adverse events, and 1 patient did discontinue the trial, but this was due to an unrelated adverse event. Ninety-four and a half percent of patients completed all expected treatments.



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