Clavis Pharma, announces that its partner, Clovis Oncology, Inc., has recruited the first patient into a Phase II clinical study (CO-101-003 study) with CP-4126 (also known as CO-101). This trial will investigate the use of CP-4126 as a 2nd line treatment for advanced, metastatic pancreatic cancer in patients refractory to 1st line gemcitabine treatment, where the mechanism of resistance is likely to be due to impaired drug entry into tumour cells.
Gemcitabine is the current standard treatment for advanced pancreatic cancer, and is also used in combination with other chemotherapy agents for the treatment of other cancers, including non-small cell lung, ovarian, gastro-intestinal and breast cancer.
The entry of gemcitabine into tumour cells has been shown to be dependent upon the expression of specific membrane transporter proteins, particularly hENT1 (human Equilibrative Nucleoside Transporter. It is estimated that, owing to deficient expression of the hENT1, at least 50% of patients with pancreatic tumours have limited cellular uptake of gemcitabine and therefore respond poorly to treatment. Published research has also suggested that hENT1 levels correlate with outcomes in lung cancer patients treated with gemcitabine-containing chemotherapy.
CP-4126 is a novel, patented, lipid-conjugated derivative of the anti-cancer drug gemcitabine, developed using Clavis' lipid vector technology (LVT). Due to its different molecular design, CP-4126 is absorbed by cancer cells independent of hENT1 levels, which may lead to an improvement in efficacy in the poorly-served group of patients with no or low hENT1 expression.
The CO-101-003 study is a 35-patient, single arm, Simon 2- stage, Phase II multicentre study that will be conducted at US sites. Patients with advanced, metastatic pancreatic cancer will be eligible for inclusion if they were refractory to 1st line gemcitabine treatment (gemcitabine-refractory) AND their tumours show no expression of hENT1.
The primary objective of this study is to determine disease control rate (DCR or best response of complete response [CR], partial response [PR], or stable disease [SD]). CP-4126 treatment will continue will continue until tumour progression or toxicity occurs.
CP-4126 is also being evaluated as a 1st line therapy in a head-to-head comparison with gemcitabine in an ongoing Phase II, pivotal trial (study CO-101-001).
”This is a very challenging test of the ability of CP-4126 to overcome hENT1 related resistance to gemcitabine,” said Eileen M. O’Reilly, MD, Memorial Sloan-Kettering Cancer Center. “Patients whose cancer fails to respond at all to gemcitabine progress rapidly. There are no approved therapies for patients whose disease progresses on gemcitabine therapy. It would be very encouraging if we are able to at least stabilize the disease in this very difficult to treat group of patients,” she added.
Olav Hellebø, CEO of Clavis Pharma, said: "This is another significant step forward in the clinical development of CP-4126 and we are delighted with the progress made by our partner Clovis Oncology.”