GOTHENBURG, Sweden (GenomeWeb) – A team of investigators at the University of Glasgow is laying the groundwork for a new network that will recruit cancer patients for enrollment in clinical trials and will sequence their tumors upfront using a custom test panel.
The network, called "Integrating medically actionable genomics into early-phase trials" (IMAGINE), should commence operations in coming months, according to Susie Cooke, head of medical genomics at Glasgow Precision Oncology Laboratories (GPOL).
Patients who enroll will have their samples tested as part of routine diagnostic care, making it easier for them to take part in clinical trials without additional testing.
Cooke described the nascent network during a talk at the European Society of Human Genetics meeting, held here this week.
GPOL is housed within the University of Glasgow's Institute of Cancer Sciences and is the partner lab for Precision-Panc, a separate clinical trials network that works with the UK National Health Service to match people with pancreatic cancer to the trial most appropriate for them.
In 2017, Cancer Research UK granted £10 million ($12.6 million) to Precision-Panc, which has since assembled a network of 20 hospitals that offer precision medicine clinical trials to patients. According to Cooke, Precision-Panc has enrolled more than 100 patients since it commenced operations at the end of 2017. All patients are tested with a custom sequencing panel designed using Agilent Technologies' SureDesign service.
Cooke stressed that the new IMAGINE and Precision-Panc networks are separate projects with two different investigative teams. IMAGINE will initially only serve patients in the west of Scotland, though it has aspirations to develop into a UK-wide network like Precision-Panc. IMAGINE will be managed through the Glasgow Clinical Trials Unit and will match patients to Phase I trials. The premise of sequencing of patients up front using GPOL's panel, though, is the same.
"By screening once for a whole array of trials, you keep your screening costs manageable," Cooke said. Patients often approach trials, are biopsied, have their samples sequenced, and then learn they are ineligible for enrollment, she noted. They are then forced to repeat the process whenever they go to enroll in other trials. By enrolling in IMAGINE, as in Precision-Panc, they will be tested reflexively, meaning they won't require further testing as they are matched to clinical trials.
"You just screen them once," said Cooke. "That keeps costs manageable and timeframes manageable."
Cooke declined to comment on funding for IMAGINE at this time. She also noted that the custom panel used in IMAGINE will differ slightly from the one used to test pancreatic patients in Precision-Panc, as IMAGINE is not focused on any specific cancer.
"The panels are slightly different at the moment — Precision-Panc has a version of our panel with a few extra pancreas-specific features, and IMAGINE has a broader set of genes to support the diverse range of tumor types we expect," Cooke said. Cooke added that GPOL may consolidate the panels in the future to simplify its workflow. Both IMAGINE and Precision-Panc rely on an analytical pipeline developed specifically to support its genomic assays, she said.
When designing its panels, GPOL opted for broad coverage, and included content for surveilling cancer gene mutations, copy number changes, disruptive structural variants, fusion genes, and. mutational signatures. It also chose to include markers for human leukocyte antigen typing, measuring retrotransposon activity, and quality control.
"We wanted a very broad assay — not a lung panel or a colorectal panel — but a broad assay that could support really diverse trials including across tumor types, and [that could] capture genomic features that are not on conventional panels," Cooke said of GPOL's design.
The panels were also designed to be, in Cooke's words, "real-world compatible." Most biopsy material is the UK is formalin-fixed and paraffin-embedded, she noted.
"The majority of clinical cancer samples still end up as FFPE blocks, so if we can accommodate that in our assays then it lowers the barrier for getting the trials up and running, maximizes the number of patients who will have samples eligible for the trial, and also lowers the barrier for subsequent clinical adoption," Cooke noted.
GPOL has to be ready to turn around samples quickly, as some patients, such as those with pancreatic cancer, have a limited amount of time for participating in clinical trials.
"There is a real challenge with pancreatic patients because the disease tends to present late and is aggressive, they deteriorate very quickly, and often that window of opportunity to get them into a trial is quite short," Cooke said.
Thanks to investments in the analytical pipeline related to Precision-Panc — from biopsy collection to downstream analysis — Cooke said that GPOL now has a low rate of attrition in regards to patient samples. All of the samples are sequenced using GPOL's setup, which includes an Agilent Bravo Automated Liquid Handling Platform for library preparation automation, and Illumina's Novaseq, HiSeq4000, and NextSeq instruments for sequencing.
GPOL also maintains its own in-house bioinformatics platform, which combines open source and in-house developed algorithms.
"From the sequencing perspective, it's been exciting, how well it's worked," said Cooke. "We have a high success rate for sequencing and generating meaningful results for these patients."
Cooke noted that IMAGINE has not yet recruited anyone and at first expects to enroll just a few cases a week. The network is expected to begin operating in the next few months.
Cooke added that investigators plan to use the data from IMAGINE, as with Precision-Panc, for research purposes as well, as well as to potentially develop new biomarkers.