About bile duct cancer
The bile duct drains bile from the liver into the small intestine. Bile duct cancer is a relatively rare cancer with an annual incidence of 1-2 cases per 100,000 in the Western world. The incidence rate has been rising worldwide over the past several decades. Survival is less than 25% at 2 years in patients with resectable tumour and less than 1% at 2 years in patients with unresectable tumour. Biliary tract sepsis, liver failure and/or malnutrition and cachexia due to locoregional effects of the disease are the most important causes of death.
Current treatment regime
Currently, surgery is the only curative option for these patients; yet the majority of the tumors are inoperable at presentation. Inoperable patients are treated with stenting to keep the bile duct open and with chemotherapy. There is no approved treatment, but the combination of gemcitabine and cisplatin has shown activity and has become standard treatment in some regions. There is a high need of better treatments to increase overall survival and quality of life.
fimaCHEM in the treatment of bile duct cancer
Bile duct cancer has been chosen as the first indication for fimaCHEM, as there is a clear medical need for better local treatment, access with light is easy by using standard endoscopic treatment procedures and the most used cytotoxic agents, gemcitabine, is one of the drugs that is significantly enhanced by PCI in preclinical studies. Fimaporfin has been granted Orphan Designation for this indication in EU and in USA.
A multi-centre Phase I dose-escalation study in 23 patients to assess the safety of fimaporfin (Amphinex®) induced PCI of gemcitabine, followed by systemic cisplatin/gemcitabine, has recently been completed in patients with inoperable extrahepatic bile duct cancer. The primary objective was to determine a tolerable dose for local bile duct treatment with fimaporfin induced PCI of gemcitabine, but the study also provided encouraging early signs of efficacy that support further clincal development in this orphan indication. Based on the positive Phase I data, the pivotal RELEASE study with registation intent was initiated and the first patient was enrolled in May 2019.
The pivotal RELEASE study design is based on the outcome of meetings with the two leading regulatory authorities, the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA). The study programme consists of a single open randomised two-arm study with 186 patients (93 patients per arm), having a control arm with the standard of care (SoC) treatment of up to eight cycles of the chemotherapies gemcitabine and cisplatin, and an experimental arm with up to two fimaCHEM treatments in addition to SoC. The study’s primary endpoint is progression free survival (PFS), with overall survival (OS) as a key secondary endpoint. The study includes an interim analysis of PFS (after 60 events) followed by analysis of objective response rate (ORR), with the potential of accelerated/conditional marketing approval as a first-line treatment for inoperable extrahepatic bile duct cancer.