Dr. Mitra on Nadofaragene Firadenovec Plus Anti–PD-1 Therapy in BCG-Unresponsive NMIBC

Anirban P. Mitra, MD, PhD, fellow, Department of Urology, The University of Texas MD Anderson Cancer Center, discusses data from an assessment of PD-1 and PD-L1 status on transurethral resection (TUR) specimens collected from patients with non–muscle-invasive bladder cancer (NMIBC) who received nadofaragene firadenovec as part of a phase 3 trial (NCT02773849).

Prior data from the trial showed that intravesical nadofaragene firadenovec was efficacious in patients with Bacillus Calmette–Guérin (BCG) unresponsive NMIBC. For the analysis presented during the 2022 American Urological Association Annual Meeting, investigators set out to examine the rationale for combining the gene therapy with an anti–PD-1 therapy like pembrolizumab (Keytruda) in this population.

TUR specimens were collected at the time of enrollment, after 12 months of treatment with nadofaragene firadenovec or upon withdrawal from the study, according to Mitra. PD-1 and PD-L1 status were assayed pre- and post-study. Although there was no statistically significant difference observed between the baseline status of these markers between responders and non-responders, a higher percentage of non-responders were found to have an upregulation of PD-1 and PD-L1 in tumor-infiltrating lymphocytes, Mitra says.

Since PD-1 is the target for pembrolizumab, these findings fuel the hypothesis that the addition of pembrolizumab to nadofaragene firadenovec could benefit patients with high-grade, BCG-unresponsive NMIBC who do not achieve complete responses to nadofaragene firadenovec alone, Mitra concludes.