1061TiP - First-In-Man Phase I Study of Tpcs2a-Based Photochemical Internalisation (PCI) of Bleomycin in Locally Recurrent or Advanced/Metastatic, Cutaneous or Subcutaneous Malignancies

Abstract

ABSTRACT Objective PCI is a novel technique in which chemotherapeutic cytotoxicity is enhanced with a photosensitiser and light exposure. This dose-escalation study assessed the safety and tolerance of TPCS2a (tetraphenyl chlorin disulphonic acid, Amphinex®) in bleomycin PCI, pharmacokinetic profiles, and determined the maximum tolerated dose (MTD). Method Cohorts of 3 to 6 patients were enrolled and the TPCS2a dose escalated by a pre-specified amount until dose-limiting toxicity (DLT) occurred in at least two patients (≥33%). Patients received TPCS2a at a starting dose of 0.25mg/kg. Four days later they received bleomycin (15,000IU/m2 IV) and after 3 hours red light laser (652nm) was applied to target lesions for 600 seconds to initiate a therapeutic response. Patients were followed for 3 months. Results Nineteen patients were enrolled: 4 with cutaneous breast cancer, 13 squamous cell carcinoma (SCC) of head and neck and other regions, 2 other cancers. 17/19 patients experienced 94 AEs, most commonly pain, photosensitivity and nausea. Most (83%) were mild or moderate. Fourteen episodes of pain (3 severe) were treatment-related. Mean patient-reported pain using a VAS scale declined from 4.9 to 1.3 24 hours after treatment. Four patients experienced skin photosensitivity reactions; 3 were in the highest dose cohort. 10/19 patients experienced 15 serious adverse events: 3 (swelling, and blistering of hands, tongue oedema) were probably related to treatment. The MTD of TPCS2a was found to be 1.5mg/kg. At day 28, 11/16 patients had a complete response (CR) in target lesions, 2 had a partial response (PR), 2 had stable disease (SD) and 1 had progressive disease (PD). At last visit there were 8 CRs, 2 PRs, 2 SDs and 2 PDs. During the course of the study four patients died (no relation to treatment) and six were withdrawn prematurely. Conclusion With appropriate analgesia and anaesthesia TPCS2a-based PCI of bleomycin was well tolerated in these patients with locally advanced cancer. Treatment-related AEs were as expected and can be managed. Preliminary efficacy data are very encouraging and a phase II study in HNSCC has just begun. Disclosure All authors have declared no conflicts of interest.