(UroToday.com) The 2024 SUO annual meeting included a urothelial carcinoma session, featuring a presentation by Dr. Mark Tyson discussing BOND-003 Cohort P, a multi-national, single-arm study of intravesical cretostimogene grenadenorepvec for the treatment of high-risk, papillary only, BCG-unresponsive non muscle invasive bladder cancer (NMIBC).
The current AUA guideline recommendation for patients diagnosed with BCG-unresponsive high risk NMIBC is radical cystectomy. However, many patients are unwilling or unable to undergo a radical cystectomy due to patient preference or competing medical risks. While the US FDA has recently approved therapies in this disease state, a considerable unmet medical need still exists for additional clinically effective, well-tolerated, and readily available bladder-sparing options.
This is particularly relevant in the BCG-unresponsive Ta/T1 without CIS population, which may comprise a majority of BCG-unresponsive high risk NMIBC patients. Cretostimogene grenadenorepvec is an oncolytic immunotherapy designed to selectively replicate in bladder cancer cells with Rb-E2F pathway alterations, commonly found in BCG-unresponsive high risk NMIBC. In addition, cretostimogene also expresses GM-CSF adding to local and systemic cancer control:
Cretostimogene received both US FDA Fast Track and Breakthrough Therapy Designations in the BCG-unresponsive high risk NMIBC CIS with or without Ta/T1 tumor indication and has demonstrated a consistently favorable safety profile with only grade 1-2 adverse events. Based on the strength of these data, the BOND-003 Cohort P study was designed as a multi-national, single-arm, clinical trial to assess the efficacy and safety of intravesical cretostimogene in BCG-unresponsive high risk NMIBC patients with Ta/T1 tumors without CIS.
Eligibility criteria for BOND-003 Cohort-P are as follows:
- Age ≥18 years
- ECOG performance status of 0-2
- Histologically confirmed BCG-unresponsive HG Ta/T1 papillary disease without CIS within 90 days of study enrollment
Patients are required to have previously received adequate BCG by the US FDA definition. Patients who recur with a HG Ta/T1 tumor within six months of the last dose of adequate BCG or who recur with HG T1 after a single induction course of BCG may be eligible. Patients must have no evidence of residual bladder cancer before treatment:
Patients will receive intravesical cretostimogene in combination with DDM, a transduction agent, adjuvant to TURBT for six weekly doses during the induction phase, followed by three weekly maintenance cycles quarterly through month 12, then every six months through month 36. Re-induction is permitted and the study administration is highlighted below:
Primary disease assessments include serial cystoscopy, urine cytology, axial imaging, mandatory biopsy at month 12, and centralized review of pathologic samples. The primary outcome measure is all-cause event free survival. Secondary outcome measures include:
- High- and low-grade recurrence free survival
- Progression free survival
- Radical cystectomy-free survival
- Bladder cancer specific survival
- Safety
- Tolerability
- Time to next intervention
Exploratory outcome measures include health-related quality of life, and biomarker analyses. Descriptive statistics will summarize patient characteristics, treatment administration/compliance, efficacy, safety, and laboratory or exploratory parameters. It is expected that enrolled patients will result in adequate confidence interval precision for comparisons to historical and published data in the BCG-unresponsive HG Ta/T1 without CIS disease state, a patient population with considerable unmet medical need. There are 35+ clinical sites that have been selected in the United States and Japan, and screening and patient selection have been initiated.
Presented by: Mark Tyson II, MD, MPH, Urologic Oncologist, Associate Professor of Urology, Mayo Clinic, Scottsdale, AZ
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Wellstar MCG Health, @zklaassen_md on Twitter during the 2024 Society of Urologic Oncology (SUO) Annual Meeting, Dallas, TX, Tues, Dec 3 – Fri, Dec 6, 2024.