By Paul Nicolaus
August 8, 2017 | The war waged against cancer gained added thrust in early 2016 when the White House Cancer Moonshot set out to take research from ground level to whole new heights, and as the senior director of external partnerships, Lauren Leiman found herself on the front lines.
It was the process of thinking back on one of her earlier roles, though, that helped propel the initiative forward. While working for the Melanoma Research Alliance, Leiman heard about a blood test that would be able to detect this most serious form of skin cancer and determine how to treat it.
That memory in mind, she asked around to find out what ever happened with that technology that hadn’t gone on to become a reality. “My colleagues from the NCI said here’s a bunch of papers. Read them. Let me know what you think,” she recalled.
When she studied those papers she did so through her own lens—one that was shaped by the teachings of an MBA as opposed to an MD or Ph.D.—and soon realized that a big part of the problem was the lack of information sharing. Although the liquid biopsy field was moving forward, progress was sluggish because the collaborative element was missing.
But what if key players in this space worked together and shared their data? The thought was far-fetched, perhaps a bit like the concept of walking in space before Neil Armstrong touched foot to moon back in ’69. Despite the magnitude of that what if, she shared it aloud at an August 31, 2016, sit-down with the Food and Drug Administration (FDA).
“They kind of said, ‘Sure, it’s a great idea, good luck with that,’ and laughed me out of the room,” she said. But that glimmer of possibility only fueled the fire. “I think in my naiveté I kind of thought, ‘Wow, they just told me to do it, so I guess I should go do it.’”
A couple of weeks later she met with roughly a dozen representatives from foundations, higher educational institutions, and industry to consider the same possibility. Following several hours of conversation, everyone around the table believed this type of collaboration could, indeed, speed progress.
“So we had an initial commitment around that table,” Leiman said, “and we moved forward very quickly after that.” A Moonshot fact sheet released October 17, 2016, outlined the contributions pledged by those involved at the time of inception.
Facing a changing White House administration, the group decided to forge ahead by forming its own organization and becoming a consortium dubbed the Blood Profiling Atlas in Cancer (BloodPAC), which is managed by the Center for Computational Science Research, Inc. (CCSR) —an Illinois-based not-for-profit corporation.
As executive director, Leiman heads up the effort to harness the collective expertise of roughly three dozen academic, government, biotechnology, diagnostic, and pharmaceutical entities with an eye on accelerating the development and approval of liquid biopsy diagnostics.
The Draw of Blood Draws
The appeal of using a simple blood draw to detect and fight cancer is clear considering the drawbacks of traditional methods, which rely on discovering a tumor and then slicing off a tissue sample.
Those tissue biopsies are pricey, invasive, and potentially risky. While some cancers are easy to access, others take root deep inside the body and getting at these tricky tumors can be both challenging for doctors and dangerous for patients.
Simple blood draws, on the other hand, could become a powerful option for better detecting and managing the disease. Patients could forget about the cut of a razor blade, and medical professionals could benefit from a more informative approach.
Because tumors shed cells and chemical signals into the bloodstream, they leave a trail of breadcrumbs that can illuminate everything from a cancer’s tissue of origin to its evolutionary state. Blood analysis can already identify the best treatments for certain types of cancer and help with the process of swapping out therapies as mutation occurs.
Roche’s cobas EGFR Mutation Test v2 is used as a companion diagnostic test (CDx) for the detection of epidermal growth factor receptor (EGFR) gene mutations. It is able to identify lung cancer patients who could benefit from Tarceva (erlotinib) and detect the T790M mutation to match patients with Tagrisso (osimertinib). But so far, it’s the only cancer liquid biopsy to receive an okay from the FDA.
Although an array of companies has blood-based biopsies on the market, the broader adoption will hinge on the ability to create more sensitive, accurate tests and then prove that they bring value to patients. Only then can the high hurdle of payer reimbursement be overcome. Meanwhile, clinicians’ hands largely remain tied.
Building a Blueprint
Boosted by the Moonshot’s mantra of a decade of progress in half the time, BloodPAC is looking to change this status quo. The consortium has formed three central working groups to help transform the liquid biopsy space and quicken its pace.
The data working group focuses on providing a data commons to store, harmonize, and analyze blood profiling information submitted by member organizations. The Open Commons Consortium (OCC) and the University of Chicago made it possible to stand the database up initially, and the first tranche of data was contributed in early December 2016.
“The real work came with what we would consider the normalization of the data,” said Jake Vinson, co-chair of the data working group and CEO of the Prostate Cancer Clinical Trial Consortium (PCCTC), a multicenter drug and biomarker development organization that spawned out of the Memorial Sloan Kettering Cancer Center.
Another significant finding was the realization of the subtle yet important differences in how data labels were being handled across the contributing datasets. Because these minor differences can create major headaches when it comes time to perform cross dataset evaluation, the data team created subgroups to focus on standards and quality. Minimal technical data elements have since been proposed, which will help standardize the process as the dataset continues to grow.
Meanwhile, the sample working group has created standards for the collection of blood profiling samples and ensured that information is contributed using the structure put in place by the data working group.
Many of the individual stakeholders have their own development programs for liquid biopsies, whether it is circulating tumor cells (CTC), cell-free DNA (cf-DNA), or other analytes using mass spectrometry, explained Phillip Febbo, co-chair of the samples working group and CMO at Genomic Health.
“Many of us are asking the same questions,” he said. The challenge put forth by Leiman was to share that data across the development spectrum so that there could be less duplication of effort.
Although there tend to be reservations on both the academic and industry side when it comes to that level of sharing, the hope is that a group effort will make it possible to more efficiently develop the performance of these types of assays and understand where they add value.
A medical oncologist by training, Febbo’s background helps bridge the divide between academia and industry. He previously spent 20 years in education, including faculty roles at Duke University and the University of California, San Francisco before joining Genomic Health, a company using new technologies to address unmet clinical needs in oncology.
“These are samples that have been put together and have been analyzed with next generation sequencing and other technologies,” he said. “They are not trivial or inexpensive, and yet already over 2,000 samples are in the database to start working on the data mining.”
The technology applications working group needs to fit right in-between the samples and data working groups, explained co-chair Peter Kuhn, a professor of biology, medicine, and engineering at the University of Southern California (USC). The goal is to build a bridge between the sample and the data on the other end.
“Obviously there are no challenges in my world,” he joked. “It’s all pretty straightforward.”
He and his group take high-complexity research approaches and then distill that down to best practices that could be implemented in patient care. Along the way, they have remained focused on building the reproducibility of the individual assays and finding ways to ensure the maximum use of samples.
Pilot Studies Underway
In partnership with the Murtha Cancer Center at Walter Reed National Military Medical Center, Kuhn is leading a half-million-dollar study funded by the Breast Cancer Research Foundation. The other BloodPAC pilot study underway is funded by the Prostate Cancer Foundation, led by Howard Scher with Memorial Sloan Kettering Cancer Center, and run through PCCTC.
The first clinical trial will send protocols to the College of American Pathologists (CAP) for review, critique, and then fine-tuning along with BloodPAC leadership. The clinical data elements also undergo a review process.
The thought is that this guidance from the regulatory agencies, data standards groups, and technique experts will allow BloodPAC to set baseline standards that lead to a common jumping off point for different types of blood-based biomarkers. This allows everyone to recreate the same datasets and get started with their development process.
These protocols then become available through BloodPAC to the entire community, Kuhn said. It creates a blueprint on top of which it is possible to rebuild over and over again, all while refining the process moving forward.
Mutually Beneficial
The value proposition for those participating in BloodPAC is an element that the leadership team must continually bring to the forefront, explained Vinson. As part of that effort, common challenges pertaining to blood-based biomarker development are identified from the academic discovery side, the clinical operation side, and the commercialization side.
Uncovering the issues that stand in the way of making progress and figuring out how those participating in the community can contribute to solving those challenges for the greater good of the organization is what leads to progress and shared benefits. “We look for those lowest common denominators that everybody has to address but oftentimes doesn’t address in a consistent way,” he said.
The collaboration taking place could eventually lead to benefits for a whole range of interested parties. Patients could gain earlier access to blood-based tests to detect and characterize cancer, and physicians would be able to monitor patients more frequently and make better-informed decisions.
Meanwhile, researchers would have access to very early-stage information along with insights into what has not worked, and the knowledge base formed along the way will help develop the evidence needed to support an FDA approval and payer reimbursement.
And industry could cash in on a massive pot of gold at the end of the rainbow. Illumina leadership has previously estimated the market value will be $20 to $40 billion if a test can detect stage 2 cancer and $100 to $200 billion if it can detect stage 1 cancer.
Other figures, while slightly less jaw-dropping, are still impressive. J.P. Morgan healthcare analysts have predicted that the liquid biopsy market could be worth as much as $20 billion by 2020, and investment firm Piper Jaffray pegged the potential value of the cancer liquid biopsy market at $29 billion, according to a 2015 report.
Market research firm Kalorama Information says the efforts to improve collaboration and information sharing between U.S. public and private sector researchers could also lead to the development of universal CDx used for the detection of a group or panel of disease-related gene mutations that replace mutation-specific molecular assays.
This could help reach more patients, avoid multiple tests and potentially reduce per-test costs. But plenty depends on the pace of discovery and regulation since there has not been a multiplex or panel CDx approved by the FDA to date. Tough review could be expected for this type of product since it would involve bypassing individual tests and, in turn, heavily impact patient outcomes.
Difference Maker
Despite the swirl of uncertainty that remains in the liquid biopsy space, there is an element that may give BloodPAC a leg up.
Instead of approaching the FDA on the back end, there was an intentional move to share the vision from the get-go and invite the agency to walk hand in hand along the way. The collaborative that has come about since then is fundamentally unique because of this dynamic, Leiman said, and it could wind up being the difference-maker.
The hope, she added, is that other groups will be able to take this model and use it to drive forward their areas of interest—whatever the disease, whatever the technology.
Paul Nicolaus is a freelance writer specializing in health and medicine. Learn more at www.nicolauswriting.com.