A first in human study using photodynamic therapy with Redaporfin in advanced head and neck cancer.

Abstract

e14056 Background: Photodynamic therapy (PDT) may be an appealing approach when head and neck cancer (HNC) patients (pts) develop locoregional standard treatment failure. Currently available systemic photosensitizers (PST) present several limitations, such as longstanding photosensitivity. Redaporfin is a new PST specifically designed to achieve improved efficacy and safety over existing options. Methods: This phase I/IIa clinical trial had the objective to determined Redaporfin tolerability, anti-tumor effect and pharmacokinetics (PK). “Dose-finding phase”: each patient was submitted to a single-ascending dose of Redaporfin, administered by iv infusion, lasting 10-20 minutes, in ≥ 21 days interval; drug was titrated up to a dose that, in combination with a laser light of 50 J/cm2 at 749±3 nm, was safe and caused tumor necrosis (“effective dose”) in a spot of 1.0 cm of diameter of tumor surface. “Final PDT session”: all accessible tumor was treated with the individual effective dose. Results: Thirteen pts (10 men, 3 women; median age 62 yrs; range 35-80) with advanced HNC in symptomatic treatment were submitted to Redaporfin doses: 0.05 mg/kg (n = 6), 0.1 mg/kg (n = 4), 0.25 mg/kg (n = 2), 0.5 mg/kg (n = 4), 0.75 mg/kg (n = 6) and 1.0 mg (n = 1). Treatment-related adverse events (TRAE): 2 pts had grade (G) 3 photosensitivity reaction (PR) after accidental exposure to intense sun-light (0.75 mg/Kg dose); G≤2 TRAEs in 7 pts (G2 infusion-related reactions in 2 pts and PR in 2 pts). Photodynamic effect was observed in all subjects at doses ≥ 0.5 mg/kg and was dose-dependent; 0.75 mg/kg dose caused necrosis in 1 cm diameter target spot deeper than 5 mm. The patient submitted to final PDT session achieved complete tumor necrosis of treated area. PK showed to be linear; drug was eliminated from the body in a relatively fast manner (half-life of 19 hrs following Redaporfin 0.75mg/Kg). Reported data allowed to conclude phase I part of the trial; next steps of clinical development were authorized. Conclusions: Redaporfin effective dose was established at 0.75 mg/Kg. PDT with Redaporfin revealed anti-tumor effect and was safe in patients with advanced HNC. Further research with this promising compound is ongoing. Clinical trial information: NCT02070432.