NEW YORK – Swiss firm Sophia Genetics shared some of the first public data on its internal validation and experience onboarding early adopters for the comprehensive liquid biopsy and solid tumor sequencing kits generated through its partnership with Memorial Sloan Kettering cancer center.
MSK has been known for years as a leader in the cancer sequencing market, with its flagship comprehensive tumor sequencing test MSK-IMPACT, and follow-on liquid biopsy panel MSK-ACCESS.
The cancer center partnered with Sophia in early 2023 with the initial focus on creating a distributable kit version of the MSK-ACCESS assay. That program grew over the last two years to also include development of the MSK-IMPACT tissue test as a kit, with AstraZeneca joining as a third partner to help distribute and promote the products.
During a Wednesday "Precision Oncology Showcase" meeting sponsored by Sophia, discussants from the company and MSK also disclosed that they are planning the same for MSK's hematologic cancer sequencing panel.
Although precision medicine has blossomed in the oncology community over the last decade, the most advanced and comprehensive tests have remained inaccessible to many outside the highest-tiered institutions. Commercial firms offer the opportunity for doctors to send out samples for broad sequencing, but many smaller health systems have a desire to offer their own in-house testing.
Building a comprehensive sequencing test from scratch may be daunting, hence the market for products that allow an institution to implement systems that have already been validated and proven in the clinic.
MSK's sequencing approach differs from many other offerings in that it involves paired tumor and germline sequencing. Being able to directly compare the two allows for precise determination of which variants are coming from the tumor and which may represent a process called clonal hematopoiesis, which occurs in normal, noncancerous cells.
During the meeting, MSK molecular geneticist Michael Berger said that the center recently sequenced its 100,000th tumor tissue sample with MSK-IMPACT and has run about 14,000 MSK-ACCESS liquid biopsy tests since launching it in 2019.
According to Berger and colleagues, the benefit in disseminating kits isn't just to the customers interested in implementing their own in-house genomics but also to MSK itself and partners like AstraZeneca.
For instance, the wealth of data from tests performed across a larger population and a more diverse set of ancestries can help improve variant analysis and help contextualize future results, Berger said.
"In terms of test performance, I think having larger cohorts already profiled on the same assay, particularly across different ancestral populations that might have different frequencies and alterations, means we can better put in context the results of a future test and be more accurate," he said.
"One of the things that the larger datasets also allow us to do is find less common hotspot mutations, but things that are still significantly mutated above what we'd expect by chance. And we've been using that statistical property to identify likely functionally relevant mutations and using that as the basis for enrolling patients onto clinical trials," Berger added.
"That statistical power will improve as we generate more data and ability to study and learn from different subsets of cancer patients," he said. "Even with 100,000 tumors, for a lot of questions, we want to ask if we're [more limited] than we want."
Sophia Genetics Senior NGS Scientist Florian Klemm described some of the work that went into translating the MSK-ACCESS test to its own internal software and reagents, which power the kit version now marketed as "MSK-ACCESS powered with Sophia DDM." This involved comparing every step to demonstrate equivalence to the parent assay.
He shared data from a head-to-head comparison using 48 clinical samples that were previously analyzed using MSK's in-house test.
"Across the target space that we were interrogating, we had very uniform coverage," Klemm said. Out of a total of 159 variants identified by MSK, the Sophia kit was able to detect 158, representing a sensitivity of 99.4 percent.
"Obviously it's not just about being correct and being able to determine or to report the same variants. It's equally important whether we are able to be precise, [and] whether we can report the same allele frequency," Klemm added, saying that the team was pleased to see a very close match.
Michael Frank, director of digital health business development and licensing at MSK, said that the partnership with Sophia wasn't the first time MSK had tried to partner to expand MSK-IMPACT and MSK-ACCESS. Several years ago, the center worked with a large reference lab, spending a year trying to get the tests running but couldn't get over about 60 percent concordance.
"The team basically didn't have the technical chops to make it work," he said.
Other companies have also come to the cancer center offering to partner to bring in more volume, but the practicalities of increasing throughput were impossible. "MSK is based in Manhattan. We don't have a lot of room. We can't just increase the number of tests," Frank said.
"A distributed kit solves the problem of how [to] amplify these tests outside of the confines of a Manhattan lab, [and] I think … 99 percent concordance speaks volumes of the technical team."
The next step, Klemm said, was to release the kit "into the wild." Something Sophia prides itself on, he said, is its customer support and early-access programs. The company's program, called MaxCare, has involved more than 500 sites overall, and according to Klemm, seven have already signed on to pilot MSK-ACCESS that have completed or are close to completing their onboarding of the kit.
Klemm said that there is also a long line of institutions waiting to join these initial seven, which is representative of the work that AstraZeneca has been doing under its partnership with Sophia and MSK to drive adoption, especially outside the US.
Sharing a little of the data from the initial adopters, Klemm described how it was able to help one institution that wasn't seeing the right number of duplex molecules in initial quality control testing. The company was able to help the center identify and correct the causal step in its library prep protocol, bringing the numbers in line.
All the sites validated their performance across matched reference samples, with sensitivity ranging from 95 percent up to 100 percent and an overall positive agreement of 99 percent.
"There is a set of variants that you see we miss in quite a few of these sites, and this is something we did not see in our initial development," Klemm said, "But this is something that is another good example of how we can actually make use of the data that our clients generate to continuously work on improving our algorithms."
For example, one variant that was missed could be tracked to a "noisy" genomic area that was challenging for the company's sequencing algorithms. A software update addressing the issue is now slated to go out at the end of the month.
Two early users spoke at the meeting, Faisal Khan, CEO of Canadian firm OncoHelix, and Leah Thompson, a lab technician with Tennessee Oncology.
Khan described OncoHelix as a public-private partnership with the University of Calgary that hosts two fully functional labs, one in Calgary and one in Abu Dhabi, United Arab Emirates. "We do sample testing from across the world, around 14 countries," Khan said. In Canada, the firm serves five public health care programs and a nationally sponsored pharmacy program.
Prior to brining in the Sophia MSK-ACCESS test — which is currently finishing validation — OncoHelix offered a smaller panel developed by the BC Cancer Agency in Vancouver, primarily to the lung cancer patients in Canada.
Khan attributed the choice to adopt the Sophia MSK-ACCESS kit over other options to OncoHelix's multiyear relationship with Sophia, which has included bioinformatic and wet lab support for a variety of other sequencing assays, as well as the proven utility of MSK-ACCESS, especially its tumor-normal matched sequencing.
Initial validation with reference samples yielded good results, Khan said, and the company is now working to complete its analysis of clinical samples, with the plan to launch the test as an LDT for both Canada and through the Abu Dhabi lab.
Tennessee Oncology's Thompson said that it just finished its second sample batch under Sophia's MaxCare program.
With over 30 clinics spread across the state of Tennessee and additional sites in northern Georgia, Thompson said that Tennessee Oncology is one of the largest community-based cancer care networks in the US.
"We have been very interested in liquid biopsy for a long time. Currently, we are sending out, so we are super excited to bring this in-house," Thompson said.
MSK-ACCESS was attractive for three reasons, she added. Familiarity with MSK through other work in the genetics field played a role. Added to that, the lab was also already using Sophia for some of its NGS assays. "We anticipate this to be an easy implementation," Thompson said.
Finally, like Khan, she said that the unique tumor-normal sequencing also made the test attractive.
With good initial results, Thompson said that she and her team are now planning a full validation.
Thompson and Khan were joined in a panel discussion by two other users, Wojciech Swat, director of cancer genomics at BioReference Health System, and Cristovam Scapulatempo Neto, medical director of anatomy and pathology at Dasa Genomica in Brazil.
The four noted many of the same drivers for bringing a liquid biopsy solution in-house, including the value of data ownership, speed of testing, and the ability to improve the rates of patients that can be referred to approved targeted therapy or clinical trials.
Klemm emphasized once again that Sophia views its relationship with adopting labs as a two-way street. "I think the biggest benefit we can deliver to our clients is that they benefit from what we have learned through the collaboration with them. As a team, we can pay forward, so to speak," he said.
"Now that MSK-ACCESS has been released, and we're gathering with academics, we can really prove that there is a correlation between liquid biopsy and solid tissue testing," Klemm added. "We're not going to be the last one who's going to provide that answer, but hopefully it will make a big impact to try to provide a meaningful answer to that question."