New Article from journal Bladder Cancer mentions TLD1433 PDT This article deals witht current and emerging bladder cancer treatments. It includes a short section on TLD1433 PDT but only talks about the phase 1b.
Novel Delivery Mechanisms for Existing Systemic Agents and Emerging Therapies in Bladder Cancer Authors: Zhang, JJ H.a | Starr, Savannah L.b | Chamie, Karima; *
Affiliations: [a] Department of Urology, UCLA Medical Center, Los Angeles, CA, USA | David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
Journal: Bladder Cancer, vol. Pre-press, no. Pre-press, pp. 1-15, 2023
Received 16 November 2022 | Accepted 28 March 2023 | Published: 21 April 2023
PHOTODYNAMIC THERAPY
Intravesical photodynamic therapy (PDT) with a novel ruthenium-based photosensitizer TLD-1433 has recently emerged as a novel delivery mechanism for patients with NMIBC after BCG failure. The rationale behind TLD-1433 is that light activation induces the generation of cytotoxic singlet oxygen and radical oxygen species that are selective for bladder tumor cells and induces downstream antitumor immune signaling. This may be activated with a diffused laser light created by a novel device. Historically, photodynamic therapy using an intravenous injection of a porfimer sodium photosensitizer followed by intravesical application of red light has demonstrated efficacy in bladder CIS with 58% CR at 3 months [78]. However, this has not translated to widespread clinical practice because the intravenous administration of porfimer sodium is associated with morbidity including skin photosensitivity and significant bladder contracture rate. Intravesical administration of the TLD-1433 photosensitizer may reduce systemic effects. A recently published phase 1b single-arm clinical trial has investigated intravesical photodynamic therapy with TLD-1433 in patients with BCG-unresponsive disease [79]. Results demonstrated no serious AEs, with the most common grade< 2 AE of lower urinary tract symptoms. Two of three patients treated with a therapeutic dose (0.7mg/cm2) demonstrated durable CR with no evidence of disease at 18 months, and the third was diagnosed with metastatic disease within 6 months, suggesting the possible initial understaging and presence of early micrometastasis. Three patients were treated with a half dose 0.35mg/cm2 and all demonstrated persistent disease at 3 months [79]. Initial results of this novel intravesical approach to PDT is favorable, but requires additional validation before proceeding to late-phase trials and widespread adoption.