Phase 3 BOND-003 cohort C findings showed a 75.5% CR rate and durable bladder preservation in high-risk, BCG-unresponsive NMIBC.
Cretostimogene grenadenorepvec, an intravesically delivered oncolytic immunotherapy, produced durable complete responses (CRs) and bladder preservation in patients with high-risk, BCG-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS), with or without Ta/T1 disease, according to results from cohort C of the phase 3 BOND-003 trial (NCT04452591) published in The Lancet Oncology.1,2
The trial met its primary end point, with 75.5% (95% CI, 66.3%-83.2%) of patients (n = 112) achieving a CR at any time following cretostimogene monotherapy, exceeding historic and contemporary clinical benchmarks in this setting.² The 12- and 24-month duration of response (DOR) rates were 64.2% (95% CI, 52.2%-73.8%) and 60.1% (95% CI, 48.2%-70.0%), respectively, with a median DOR of at least 27.9 months that remained ongoing at data cutoff. Approximately 90% of patients who were in response at 12 months maintained a durable response at 24 months, and one patient remained disease-free beyond 51 months.
“Patients with BCG-unresponsive NMIBC often face the difficult decision between pursuing additional bladder-sparing therapies or undergoing a severe, life-altering cystectomy,” Mark D. Tyson II, MD, MPH, a professor of urology at Mayo Clinic in Phoenix, Arizona, and the lead author of the publication, stated in a news release.1 “The results from BOND-003 represent a potential shift in this treatment paradigm, underpinned by encouraging DOR and bladder preservation outcomes. With a clinically meaningful median DOR of 27.9 months, possibly among the longer DORs seen in this setting, paired with approximately 89% of patients maintaining their bladders at 12 months and 81% at 24 months, we are seeing evidence of sustained bladder preservation without compromising the window for further therapeutic options, if needed.”
BOND-003 is a single-arm, phase 3, monotherapy trial evaluating intravesical cretostimogene in a fully enrolled global population of 112 patients across sites in North America, Australia, and the Asia-Pacific region.² Enrollment required high-risk, BCG-unresponsive NMIBC with CIS, with or without Ta or T1 papillary tumors.
Eligible patients received intravesical cretostimogene at 1 × 1012 viral particles per 0.8 mL per week as 6-week induction therapy followed by maintenance. Re-induction was permitted for persistent disease at 3 months.
The primary end point was centrally confirmed CR at any time. DOR and safety were assessed as secondary end points.²
Approximately 89% of patients maintained their bladders at 12 months and 81% at 24 months. Most patients (96.6%) were free from progression to muscle-invasive bladder cancer at both 48 and 96 weeks, with an overall progression rate of 3.4%.1,2
“These data underscore cretostimogene's potential to become a foundational monotherapy for NMIBC and support our ongoing effort to explore its role across multiple disease settings, including adjuvant and combination approaches,” Vijay Kasturi, MD, chief medical officer of CG Oncology, added in the news release.¹
Cretostimogene has received FDA fast track and breakthrough therapy designations and is also under investigation in the phase 3 PIVOT-006 trial (NCT06111235) in intermediate-risk NMIBC and the phase 2 CORE-008 trial (NCT06567743) in high-risk NMIBC.
No grade 3 or higher treatment-related adverse effects (TRAEs), treatment-related discontinuations, or treatment-related deaths were reported.¹,² The median time to resolution of related adverse effect was 1 day (IQR, 0-7).
The most common TRAEs occurring in at least 10% of patients were bladder spasm, pollakiuria, micturition urgency, dysuria, and hematuria.¹ Cretostimogene does not require prophylactic anticholinergic medication, operating room time, additional cystoscopy, or anesthesia dosing, and aligns with existing AUA/SUFU intravesical administration practice patterns.
“These results are particularly encouraging given BOND-003 enrolled a heavily pretreated population representative of the patients that clinicians often encounter in real-world practice,” Tyson added in the news release. “Specifically, we observed meaningful responses in patients who had already received other therapies, including intravesical gemcitabine–docetaxel or systemic pembrolizumab, underscoring cretostimogene's activity across a clinically diverse and difficult-to-treat patient population. If approved by the FDA, cretostimogene may represent an important, bladder-sparing, advancement in the bladder cancer treatment paradigm, and meaningfully improve patient outcomes.”
