LUNAR: Safety and efficacy evaluation of nadofaragene firadenovec instilled into the renal pelvis in subjects with low-grade upper tract urothelial carcinoma—A single-arm, open-label phase 1/2 trial.

TPS906 Background: Recommended treatment options for low-grade upper tract urothelial carcinoma (LG-UTUC) include kidney-sparing surgery and radical nephroureterectomy. Kidney-sparing surgery, such as endoscopic ablation, allows the preservation of the ipsilateral kidney, but is associated with high local recurrence rates. Mitomycin gel, the first Food and Drug Administration (FDA)-approved non-surgical treatment for LG-UTUC, is associated with a risk for ureteral strictures. Therefore, there is an unmet need for an alternative well tolerated and effective localized non-surgical treatment option for subjects with LG-UTUC. Nadofaragene firadenovec is a replication-deficient adenoviral vector carrying the interferon alpha-2b (IFNα2b) transgene. It is an effective and well tolerated intravesical bladder-sparing gene therapy approved by the FDA for the treatment of adults with high-risk Bacillus Calmette Guérin (BCG)-unresponsive non-muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) ± papillary tumors. The primary objectives of the LUNAR trial are to evaluate the safety and efficacy of nadofaragene firadenovec instilled into the renal pelvis in subjects with LG-UTUC. Methods: Twenty subjects with biopsy-proven LG-UTUC and ≥ 1 measurable papillary low-grade tumor (5-15 mm diameter) above the ureteropelvic junction will be included in this marker-lesion trial. The trial will start with a safety lead-in period in a cohort of 6 subjects, before enrolment of the remaining 14 subjects. During the treatment period, subjects will participate in disease evaluation visits scheduled every 3 months, including ureteroscopy, selective urine cytology, and for-cause biopsy. The primary efficacy endpoint is complete response at 3 or 6 months, defined as the absence of any UTUC in the renal pelvis, indicated by negative urine cytology for high-grade urothelial carcinoma, and either no suspicious lesions on ureteroscopy or a negative for-cause biopsy. Secondary efficacy endpoints include duration of response and urinary excretion of IFN-α2b protein. Results from this trial are expected in 2029. Clinical trial information: NCT06668493 .