Trials launch of nadofaragene firadenovec in bladder cancer

Ferring Pharmaceuticals has announced the opening of the first clinical trial sites in 2 studies within the ABLE clinical trial program of nadofaragene firadenovec-vncg (Adstiladrin) in non–muscle invasive bladder cancer (NMIBC), the company announced in a news release.¹

Nadofaragene was approved by the FDA in December 2022.

The company also reported the launch of the phase 1/2 LUNAR trial (NCT06668493) to explore the safety, tolerability, and efficacy of nadofaragene instilled to the renal pelvis in patients with low-grade upper tract urothelial cancer (LG-UTUC).

Nadofaragene was approved by the FDA in December 2022 for the treatment of patients with high-risk BCG-unresponsive NMIBC with CIS with or without papillary tumors.

“The availability of an innovative locally delivered gene therapy has the potential to be organ sparing for appropriate NMIBC and UTUC patients,” said Joern Jakobsen, MD, PhD, Vice President and Head of Global Research and Medical for Uro-Oncology and Urology at Ferring Pharmaceuticals, in the news release.¹ “The extension of the ADSTILADRIN clinical trial program—with a focus on IR NMIBC and LG UTUC where there is a desperate need for new treatments, and generation of mono and combination therapy data, including re-induction, for high-risk BCG-unresponsive NMIBC—is key to understanding how ADSTILADRIN may be able to help even more patients.”

The first study opening enrollment within the ABLE platform includes the phase 2 ABLE-22 trial (NCT06545955), which is exploring nadofaragene as a monotherapy or in combination with chemotherapy (gemcitabine and docetaxel) or an immune checkpoint inhibitor (pembrolizumab [Keytruda]) in patients with high-risk BCG-unresponsive NMIBC. In total, the trial plans to enroll 150 patients across sites in the US.²

The primary end point is the complete response rate, assessed for up to 12 months. Secondary end points include the durability of complete response, cystectomy-free survival, overall survival, and the incidence of adverse events. Primary completion of the study is anticipated for July 2026.

Additionally, the first clinical trial sites were activated in the phase 3B ABLE-32 trial (NCT06510374), which is evaluating the safety and efficacy of nadofaragene vs observation in patients with intermediate-risk NMIBC. The randomized controlled study will enroll approximately 454 patients across study sites in the US.³

The primary outcome measure is recurrence-free survival at 24 months. The frequency of adverse events is a secondary end point. Primary completion of the trial is expected for August 2028.

Ferring has also initiated the phase 1/2 LUNAR trial (NCT06668493), which is seeking to enroll 20 adult patients with LG-UTUC.⁴ The study will begin with a safety lead-in period, instilling only the first 6 patients in the study. All patients will receive instillations of nadofaragene into the renal pelvis.

The primary outcome measures include the number of treatment-emergent adverse events as well as the complete response rate at 3- and 6-month time points. Completion of the study is anticipated for November 2029.

In addition to these 3 studies, nadofaragene is also being assessed in the ongoing ABLE-41 trial (NCT06026332), a real-world evidence study to assess the early utilization, experiences, and outcomes of the agent in the routine care setting. Patients are eligible for inclusion in the observational study if they have NMIBC and have not previously received nadofaragene in a clinical trial.

The first patient was enrolled in the study in September 2023. The target enrollment is approximately 400 patients. Final completion of the trial is anticipated for December 2025.⁵

References

1. Ferring advances three studies in ADSTILADRIN (nadofaragene firadenovec-vncg) clinical trial program. News release. Ferring Pharmaceuticals. Published online and accessed December 3, 2024. https://www.businesswire.com/news/home/20241203511070/en/Ferring-Advances-Three-Studies-in-ADSTILADRIN%C2%AE-nadofaragene-firadenovec-vncg-Clinical-Trial-Program

2. A trial to evaluate intravesical nadofaragene firadenovec alone or in combination with chemotherapy or immunotherapy in participants with high-grade BCG unresponsive non-muscle invasive bladder cancer (ABLE-22). ClinicalTrials.gov. Last updated November 14, 2024. Accessed December 3, 2024. https://www.clinicaltrials.gov/study/NCT06545955

3. Trial of nadofaragene firadenovec vs. observation in participants with intermediate risk non-muscle invasive bladder cancer (ABLE-32). ClinicalTrials.gov. Last updated November 26, 2024. Accessed December 3, 2024. https://www.clinicaltrials.gov/study/NCT06510374

4. Low-grade UTUC treated with nadofaragene firadenovec administered to renal pelvis (LUNAR). ClinicalTrials.gov. Last updated October 31, 2024. Accessed December 3, 2024. https://www.clinicaltrials.gov/study/NCT06668493

5. ADSTILADRIN early utilization and outcomes in the real world setting (ABLE-41). ClinicalTrials.gov. Last updated November 13, 2024. Accessed December 3, 2024. https://clinicaltrials.gov/study/NCT06026332