New Trials to Study Nadofaragene Firadenovec-vncg in NMIBC

Bladder Cancer, Urinary Bladder Image: © reineg - stock.adobe.com

Three new nadofaragene firadenovec-vncg (Adstiladrin) in BLadder cancEr (ABLE) clinical trials are set to begin in the US for the treatment of patients with non-muscle invasive bladder cancer (NMIBC). Plans to expand select clinical trials outside of the US are anticipated for later this year.¹

Nadofaragene firadenovec was approved by the FDA in December 2022 for adult patients with high-risk Bacillus Calmette-Guérin (BCG)-unresponsive NMIBC with carcinoma in situ (CIS) with or without papillary tumors. This marks the first and only FDA-approved intravesical nonreplicating gene therapy for patients with NMIBC.

Currently, the clinical trial program includes 5 multiyear studies to evaluate nadofaragene firadenovec for the treatment of a variety of urothelial cancers. These 3 new ABLE trials will add to the existing multiyear nadofaragene firadenovec studies program and expand the body of evidence for the agent.

“[Nadofaragene firadenovec is the foundation of Ferring's leadership mission in the uro-oncology therapeutic category and our ambition is for it to become the new standard of care and the backbone therapy for patients across the NMIBC disease spectrum,” said Bipin Dalmia, senior vice president, global head, uro-oncology franchise, Ferring Pharmaceuticals, in a press release. “Embarking on a broad research and geographic expansion program is yet another demonstration of our commitment to the uro-oncology community, together with our significant manufacturing investments that recently enabled full availability of [nadofaragene firadenovec to every appropriate US patient who needs it.”

The first trial will be the phase 2 ABLE-22 study. This randomized, multicenter, open-label trial plans to evaluate nadofaragene firadenovec alone or in combination with chemotherapy consisting of gemcitabine and docetaxel or pembrolizumab (Keytruda) in adult patients with high-grade BCG-unresponsive NMIBC. The goals of the study are to evaluate the safety and efficacy of the combination or monotherapy.

ABLE-32 is a phase 3b study of nadofaragene firadenovec vs observation in patients with intermediate-risk NMIBC. The randomized, controlled trial plans to evaluate the safety and efficacy of nadofaragene firadenovec.

Finally, the phase 4 ABLE-42 study is a multicenter, open-label trial looking to assess the efficacy of retreatment with nadofaragene firadenovec in patients who are previously treated with high-grade BCG-unresponsive NMIBC with CIS with or without papillary tumors who had not responded to the agent at the first 3-month assessment.

Additional ongoing studies within this program include the ongoing, non interventional, real-world evidence study, ABLE-41 (NCT06026332). The trial, which is evaluating the early utilization experiences and outcomes of nadofaragene firadenovec in the routine care setting, includes patients aged 18 years or older with high-risk, BCG-unresponsive NMIBC.

Nadofaragene firadenovec is being given to patients in a clinical setting and patients must have not previously received this therapy in a clinical trial. The first patient was enrolled in this trial in September 2023.

A phase 3b, single arm study in Japan (000381) is also evaluating the agent in patients with high-grade, BCG-unresponsive NMIBC.

“[Nadofaragene firadenovec] is an established monotherapy treatment option for patients with BCG-unresponsive NMIBC disease, an area where patients’ treatment options have been severely limited for decades,” said Pierre-Yves Berclaz, MD, PhD, executive vice president and chief science and medical officer, Ferring Pharmaceuticals, in a press release. “These new trials underscore Ferring's commitment to create solutions for patients by enlarging the body of evidence for this novel nonreplicating gene therapy.”

About the FDA Approval of Nadofaragene Firadenovec in BCG-Unresponsive NMIBC

Nadofaragene firadenovec is a nonreplicating adenoviral vector-based gene therapy.

The therapy was approved based on findings from the open-label, multicenter, single-arm, phase 3 Study CS-003 (NCT02773849). In the trial, nadofaragene firadenovec was effective and demonstrated a favorable risk profile in the study.^2-4

Among patients given the single intravesical 75 mL dose of nadofaragene firadenovec (3 × 10¹¹ viral particles per mL) complete responses (CRs) were achieved in 51% (95% CI, 41%-61%) of patients with CIS with or without concomitant high-grade Ta or T1 disease within 3 months. With this, the primary end point of the study was met.

The median duration of response was 9.7 months with nadofaragene firadenovec and 46% of the patients who achieved a CR were high-grade recurrence-free at 12 months.³

For safety, the most common grade 3/4 drug-related adverse event (AE) observed within the trial was micturition. This was seen in 2 patients, and both AEs were grade 3. Further, no treatment-related deaths occurred during the study.

REFERENCES:

1. Ferring adds three new studies to non-muscle invasive bladder cancer clinical trial program with ADSTILADRIN® (nadofaragene firadenovec-vncg). News release. Ferring Pharmaceuticals. April 16, 2024. Accessed April 16, 2024. https://tinyurl.com/4shkkavj

2. Ferring receives approval from U.S. FDA for Adstiladrin for high-risk, BCG-unresponsive non-muscle invasive bladder cancer. News release. Ferring Pharmaceuticals. December 16, 2022. Accessed April 16, 2024. https://bit.ly/3YxyWdY

3. FDA approves first gene therapy for the treatment of high-risk, non-muscle-invasive bladder cancer. News release. FDA.gov. December 16, 2022. Accessed April 16, 2024. https://bit.ly/3HNUI7t

4. Boorjian SA, Alemozaffar M, Konety BR, et al. Intravesical nadofaragene firadenovec gene therapy for BCG-unresponsive non-muscle-invasive bladder cancer: a single-arm, open-label, repeat-dose clinical trial. Lancet Oncol. 2021;22(1):107-117. doi:10.1016/S1470-2045(20)30540-4