Trial to evaluate novel combination in BCG-unresponsive NMIBC

A clinical development collaboration between Ferring Pharmaceuticals and Theralase Technologies has been established to evaluate the potential benefit of a novel combination regimen for patients with high-risk BCG-unresponsive non–muscle invasive bladder cancer (NMIBC) with carcinoma in situ (CIS) with or without papillary tumors (±Ta/T1).¹

Through the agreement, the parties are seeking to launch a phase 2 study of nadofaragene firadenovec-vncg (Adstiladrin) in combination with the investigational light-activated small molecule TLD-1433 (Ruvidar). The study will be conducted as part of an ongoing trial of TLD-1433 (NCT03945162) in NMIBC. Theralase will remain the sponsor of the study, with a joint development committee from both parties providing clinical overview of the new cohort.

"The introduction of Adstiladrin, as the first intravesical gene therapy, has filled a critical unmet need for patients with BCG-unresponsive NMIBC who faced limited treatment options and needed an alternative to invasive bladder removal surgery,” said Ashish Kamat, MD, MBBS, FACS, Endowed Professor of Urologic Oncology (Surgery) and Cancer Research at University of Texas MD Anderson Cancer Center, Houston, Texas and President of the International Bladder Cancer Group, in a news release from Ferring.¹ “As the BCG-unresponsive treatment paradigm continues to evolve, the combination of complementary therapies may offer additional treatment options to definitive therapy. This new study offers an opportunity to explore the possibility of enhancing efficacy and durability of response with a combination of a promising, investigational, light-activated small molecule with the leading gene therapy in NMIBC.”

Nadofaragene is a non-replicating adenoviral vector-based gene therapy indicated for patients with high-risk BCG-unresponsive NMIBC with CIS with or without papillary tumors. The agent was approved based on a clinical trial program (NCT02773849) that included 157 patients across 33 US sites. At 5-year follow-up, treatment with nadofaragene allowed for bladder preservation in 49% of patients (95% CI, 40 to 57.1), and overall survival was 80% (95% CI, 71 to 86).²

TLD-1433, according to the news release, is “an investigational small molecule that penetrates cancer cell walls and, upon light activation, delivers targeted cytotoxic effects to destroy cancer cells, while inducing immunogenic cell death, stimulating both innate and adaptive immune responses.”

The phase 2 trial of TLD-1433 has enrolled and treated 88 of 90 patients with BCG-unresponsive disease with CIS. Theralase plans to complete enrollment of the remaining 2 patients in the first quarter of 2026. Follow-up in the main study is expected to reach completion by the second quarter of 2027.

In the new collaborative cohort, patients will receive the intravesical photodynamic therapy followed by treatment with nadofaragene.

“Underscoring our ambition to establish ADSTILADRIN as the backbone therapy in NMIBC, this collaborative clinical study with Theralase aims to explore whether combination approaches can further enhance patient outcomes, building on the strong foundation ADSTILADRIN has established in treating this challenging disease,” said Daniel Shoskes, MD, MSc, FRCS (C), Vice President and Global Medical Director for Uro-Oncology, Ferring Pharmaceuticals, in the news release.¹

Roger DuMoulin-White, BSc, P.Eng, Pro.Dir, President, CEO, and Chairman of the Board of Theralase, added, "We are honored to collaborate with Ferring, a worldwide leader in uro-oncology with deep expertise in bladder cancer treatment. As we approach completion of our clinical study and regulatory submissions for Ruvidar, this partnership provides the perfect opportunity to investigate whether we can deliver even greater benefits to patients through innovative combinational approaches."

REFERENCES

1. Ferring Pharmaceuticals and Theralase® Technologies Announce Clinical Development Agreement to Investigate Combination Therapy in Bladder Cancer. News release. Ferring Pharmaceuticals. January 12, 2026. Accessed January 12, 2026. https://ferringusa.com/?press=ferring-pharmaceuticals-and-theralase-technologies-announce-clinical-development-agreement-to-investigate-combination-therapy-in-bladder-cancer

2. Narayan VM, Boorjian SA, Alemozaffar M, et al. Efficacy of intravesical nadofaragene firadenovec for patients with bacillus Calmette-Guérin–unresponsive nonmuscle-invasive bladder cancer: 5-year follow-up from a phase 3 trial. J Urol. 2024;212(1):74-86. doi:10.1097/JU.0000000000004020