The progress of a large pan-European clinical trial (POSEIDON) into a novel targeted study drug (called taselisib or GDC-0032) for difficult to treat breast cancers was announced today by the collaborative RATHER and EurocanPlatform projects.

The two projects are funded by the European Commission through the Seventh Framework Programme (FP7).

The three POSEIDON clinical trial centres, the Netherlands Cancer Institute (Amsterdam), Cambridge Cancer Centre (UK), and the Vall d’Hebron Hospital (Barcelona, Spain) take part in both programmes, and began to study patients treated with this investigational drug in December 2014.

Breast cancer is the most frequently diagnosed cancer in women, accounting for 25% of all female cancers, and is the second leading cause of death from cancer.

The RATHER project is focused on finding new drug targets for two types of breast cancer, invasive lobular carcinoma (ILC) and triple negative breast cancer.

ILC is an aggressive cancer that does not respond well to current treatments while triple negative breast cancer lacks the oestrogen, progesterone and HER2 receptors which are common and effective drug targets in other types of breast cancer.

These cancers account for 25% of all breast cancers, and have a very poor prognosis.

There has been considerable success in targeting gene mutations with specific drugs in other cancers, and so the RATHER project team is aiming to find other possible drug targets, by focusing on protein kinases (promising drug targets for cancer) such as PI3K, the protein inhibited by the novel investigational drug, taselisib.

Taselisib has been developed by Genentech, Inc. (a member of the Roche Group), and is an isoform-specific inhibitor of the protein PI3K.  Genes encoding PI3K are often mutated in breast cancer, particularly in ILC, suggesting that targeting these genes could effectively halt the growth of cancers that are ‘driven’ by kinases.

Professor William Gallagher, Professor of Cancer Biology at University College Dublin and Coordinator of the RATHER project emphasising the importance of this clinical trial and ongoing research into breast cancer said, “Now that the dose escalation part of the POSEIDON trial has been completed, we look forward to opening the randomised phase II part of the trial later this year to assess its effectiveness at treating hormone receptor-positive (HER2-negative) breast cancer patients. It is expected that phase II will be completed by the end of 2017, with nearly 300 patients from several European countries including the Netherlands, UK, Spain and France participating in the trial.”

The successful collaboration was highlighted by Principal Investigator Dr Javier Cortes (Vall d’Hebron Hospital), who remarked “It is impressive to see how three medical research institutions and their respective hospitals can lead together a large project with the aim of optimizing endocrine therapy in patients with advanced breast cancer. The success of the phase I part of the study and the upcoming initiation of the phase II part is an example of academic European collaboration in breast cancer.”

The joint leaders of the POSEIDON clinical trial, and members of the RATHER and EurocanPlatform programmes are Professor Sabine Linn (Netherlands Cancer Institute) and Dr Richard Baird (University of Cambridge, UK).

Professor Linn said, “We are delighted that recruitment to the POSEIDON trial is going so well; the combination of taselisib with endocrine therapy is an important new therapeutic approach to test for patients with hormone-driven advanced breast cancer.”

Dr Baird said, “This investigator-led clinical trial provides an exciting opportunity to further extend the arsenal of therapeutic weapons against breast cancer and, importantly, in a highly targeted way. Indeed, this ground-breaking clinical trial is a prime example of the prevalence and power of personalised cancer medicine.”

The EurocanPlatform coordinator, Professor Ulrik Ringborg of the Karolinska Institutet in Sweden, said “This trial is an example of how to integrate clinical and preclinical cancer research with the aim to identify not only the benefit and risk of a potential new treatment but also important biological mechanisms which will be used to personalize treatment. Further, it is an important step towards innovative collaborations between Industry and Academic Centres required for an effective drug development.”

Source: The RATHER project