Photochemical Internalisation (PCI) is a novel technology for treatment of cholangiocarcinoma

Despite the advancement of new surgical and chemotheraputic treatment options for patients with extrahepatic cholangiocarcinoma (CCA), the prognosis for patients is still poor. PCI is a novel technology which could prove to contribute to the treatment options for this patient group.

PCI is a relatively new treatment modality that can enhance the anti-tumor effect of a variety of molecules, including several commonly used cytotoxic drugs. Amphinex (TPCS2a) is a proprietary photosensitizer that is used to induce PCI. It is designed to localise to endosomal membranes and induce endosomal disruption upon light activation. Many cancer drugs and other molecules of therapeutic interest are taken up in cells by endocytosis, and ends up entrapped in endocytic vesicles. PCI can induce the release of such molecules from endosomes, thereby making it possible for them to reach their therapeutic target in the cell cytosol or nucleus. Based on positive preclinical results for PCI with gemcitabine and promising results from a phase I study with bleomycin in patients with miscellaneous cancers, it was decided to start a phase I/II study to investigate the effect of PCI with gemcitabine in patients with advanced inoperable CCA. The study is ongoing in several centers in Germany and UK. A standard 3+3 design is applied in the dose escalation, and a 5:2 randomisation into arms of stenting+PCI+Gem/Cis vs. stenting+Gem/Cis will be used in the phase II.

Preclinical experiments will be presented showing that PCI can enhance the effect of gemcitabine in an in vivo lung cancer model, and that it can also substantially increase the cytotoxic effect of gemcitabine on cholangiocarcinoma cells in vitro.

At this point 8 patients have been enrolled in the clinical study, and the 3 rd cohort is open. The treatment has been well tolerated and no serious safety concerns have been raised so far. 4 patients have experienced photosensitivity reactions, but all were mild. To date one patient has expired (at 9 Mo) due to rapidly progressing metastatic disease, all other patients are alive, including 2 patients from cohort 1 (alive 13+ Mo). More on study design, dosing schedules and preliminary safety and efficacy results will be presented.