CRUK tests drug combo for advanced pancreatic cancer

Cancer Research UK has announced it will study Plexxikon’s dual kinase inhibitor PLX7486 in combination with gemcitabine in advanced pancreatic cancer as part of its Combinations Alliance.

The novel combination of drugs targets the process of nerve invasion, observed in over 80% of pancreatic ductal adenocarcinoma (PDAC) and is associated with tumour spread and severe pain.

The PAGoDA trial will use PLX7486 to target Trk kinases, which are believed to help cancer cells invade nerves. It’s hoped that PLX7486, in combination with the chemotherapy drug gemcitabine, could improve progression-free survival and reduce pain for pancreatic cancer patients.

The study will be conducted through the Experimental Cancer Medicine Centre (ECMC) network, supported by Cancer Research UK and the UK Health Departments.

Led by the Manchester ECMC and sponsored by the University of Glasgow Clinical Trials Unit, the trial will span four sites across the UK, with the first patients expected to start treatment in early June.

Once a safe dose has been determined, clinicians will assess if the combination is able to control pain for patients and whether it has an effect on tumour growth. It’s hoped biopsies from a subset of patients will also shed light on how the drugs affect the development of both nerves and the tumours themselves.

Dr Natalie Cook, chief investigator of the trial and clinical lead of the Manchester ECMC, said: “There is still a lack of options for pancreatic cancer patients and survival remains stubbornly low. Some patients experience pain that is very difficult to control, and we know that these patients tend to do worse than those with controlled symptoms.

“Preclinical models show that giving this drug combination seems effective at stopping the cancer cells growing and multiplying. Hopefully, this will translate into clinical benefits and enable us to better control the pain and spread of cancer in patients.”

The Combinations Alliance is a Cancer Research UK supported academic-industry initiative. The alliance facilitates translation of academic research ideas into early phase combination clinical trials by working alongside both industry and researchers in the ECMC. The initiative enables research into novel drug combinations, bringing cancer patients more treatment options that otherwise would not be possible.

Only 1% of people diagnosed with pancreatic cancer in England and Wales survive their disease for ten years or more, and the treatments currently available cause significant pain as a side-effect.

Plexxikon was acquired by Daiichi Sankyo for $805 million in 2011 and is known for its tenosynovial giant cell tumour (TGCT) drug pexidartinib, which was recently approved by FDA advisors.