Breaking barriers in lung cancer biomarker testing
Biomarker testing has become increasingly critical for patient care in ensuring that non-small cell lung cancer (NSCLC) patients receive the right treatment. However, the field faces significant challenges in this testing process, including limited tissue availability and varying assay sensitivities. In this interview, we speak with Nathalie Bernard (CellCarta, Belgium) about ASPYRE – an accurate, rapid, highly sensitive assay that is able to detect a wide range of actionable NSCLC variants.
We discussed how the ASPYRE assay has been validated for use in clinical trial patient management, making precision medicine more accessible for lung cancer patients worldwide by expanding eligibility for targeted therapy trials.
Nathalie has a PhD in Molecular Biology. Following a post-doc in Montreal, Nathalie joined the industry to support PCR and sequencing platforms. She has worked in genomics for over 25 years, with a priority on supporting customers to decipher disease mechanisms and develop innovative therapies. As the Scientific Business Director of Genomics at CellCarta, Nathalie provides scientific consultation on all genomics platforms.
What targeted therapies are currently available for lung cancer patients?
Since 2011, there have been approximately 30 different targeted therapies approved for different stages of NSCLC. Typically, when a patient is diagnosed in Europe, they undergo a series of established therapies; unless a biomarker is identified, then patients might have access to targeted therapy.
Usually, the first line of treatment is chemotherapy. Unfortunately, chemotherapy works on only approximately 30% of patients. However, if the patient has a known biomarker and an existing drug for that biomarker exists, then the chances of remission are much higher, as you are using the right drug for the right patient.
Which lung cancer patients are most likely to benefit from targeted therapeutics?
Whether a patient can benefit from a targeted therapeutic or not depends on their biomarker status. Not all patients have a known, targetable biomarker in their tumor, and the frequency of biomarkers can range from a few percent for rare biomarkers such as the ROS1 mutation, which is present in a very small number of patients, to as high as 20% for more common biomarkers, such as EGFR. Accurately identifying such biomarkers is essential to getting targeted treatments to the patients who will benefit the most. However, many testing approaches can be limited in scope, with some smaller clinical laboratories focusing only on a single gene, such as EGFR, which captures only one potential target.
In comparison, we take a panel testing approach, targeting 11 genes that are known NSCLC biomarkers, and cover 98% of the recommended NSCLC biomarkers. Our work focuses on supporting our customers as they develop new therapeutics, by performing biomarker testing to identify and enroll eligible patients into clinical trials.
The ASPYRE assay has become an important tool for connecting NSCLC patients to the right investigational therapies. As a contract research organization (CRO), we collaborate closely with pharmaceutical companies during their clinical trials to conduct biomarker testing that helps them better understand their drugs in terms of which patients are most likely to respond, as well as potential side effects. With the ASPYRE assay, we have been able to bring the validation up to the standard where it can be used to manage patients. The ASPYRE assay provides insight on which patients should be included in the clinical trial.
What challenges exist in identifying which patients will benefit?
One of the main challenges is limited tumor sample availability. Biopsies at diagnosis rarely involve a large tumor resection, so by the time a patient enrolls in a clinical trial or has received several lines of treatment, the original sample is often no longer available as it is used for mandatory tests such as PD-1/PD-L1 expression. Limited tumor samples for genomic analysis adds a challenge to the identification of actionable biomarkers.
Because many biomarker assays can require a lot of sample input, this limitation is often the primary reason some patients never undergo or fail comprehensive testing. To test for multiple biomarkers, laboratories must either run several separate single-gene tests, each consuming additional tissue, or use a next-generation sequencing (NGS) panel to cover multiple biomarkers at once, which also requires a lot of sample input. The ASPYRE assay helps address this challenge because it can deliver accurate results from a limited amount of sample, and it also allows multiple biomarkers to be analyzed in a single test.
Beyond the challenge of limited sample input, local testing availability and assay sensitivity also pose barriers. Not all laboratories run full biomarker panels, and less sensitive assays can miss mutations, leaving some patients without the chance to receive a targeted treatment.
How can biomarker testing support these patients?
Accessible, accurate, and comprehensive biomarker testing is vital for ensuring that eligible patients are identified and can be subsequently matched to the targeted treatments most likely to benefit them. The ASPYRE assay is a great example of how this can be achieved, offering a highly sensitive and reliable approach to biomarker detection.
The ASPYRE assay was developed by Biofidelity (Cambridge, UK). Our team first heard about the assay through a poster they presented at the 2024 AACR Annual Meeting (5–10 April, CA, USA). Their results showed how ASPYRE rescued 98% of 106 samples that had previously failed quality control in next-generation sequencing (NGS) testing. Those were real patient samples where conventional testing had failed to detect actionable biomarkers, yet ASPYRE was able to identify them. At this point, it was a research-use-only assay, but it indicated how a more sensitive assay could make a real difference for patients who might otherwise miss out on targeted therapies. Biofidelity continues to publish data on the ASPYRE assay.
…it indicated how a more sensitive assay could make a real difference for patients who might otherwise miss out on targeted therapies.
We went on to discuss the assay with key opinion leaders within our customer network. They told us they were highly interested in ASPYRE but needed it to be validated for clinical use. To achieve that, we needed to prove that the assay could reliably detect biomarkers—a level of validation that’s essential for any test used in patient management during clinical trials. Regulatory requirements for patient management in clinical trials are understandably high, as health authorities must be confident that when a drug reaches the market, it has been tested properly and under strict quality standards. Once validated, we could use ASPYRE in clinical trials to help sponsors identify the right biomarkers and patient populations for their studies.
That’s where we play an important role. Before a therapy can be approved, it must go through several phases of testing—Phase I, II, and III trials—and we support this process by ensuring the right biomarkers and patient cohorts are selected. The importance of this approach is illustrated in AstraZeneca’s paper on the 5R framework, which outlines what is needed to bring a good drug to market. The five R’s are the right target, right tissue, right safety, right patient and the right commercial potential. The idea is that if you want to bring a drug to market, you need to make sure that you have the right biomarker and are working with the right cohort of patients.
Additionally, to focus on patients who could not benefit from approved targeted therapies, biomarker testing can be used to exclude patients from clinical trials. In these situations, assay sensitivity is especially important. When testing to exclude a patient, you want to make sure that a negative result is a true negative and not the result of an assay that simply couldn’t detect the mutation. This is another reason we were very interested in implementing ASPYRE in our clinical offering.
Ultimately, that’s how biomarker testing, and ASPYRE in particular, helps support patients. By providing a more sensitive and reliable way to identify or rule out actionable mutations, it ensures that more patients are accurately matched to the right clinical trials and, eventually, to the therapies most likely to benefit them.
What are the potential benefits of using ASPYRE technology?
One of the key advantages of the ASPYRE assay is its exceptional sensitivity. The assay amplifies selectively the mutation, helping find the needle in the haystack. This ability to isolate the mutation signal makes ASPYRE highly precise and reliable for detecting even low-frequency variants.
Another major advantage of ASPYRE is its ability to work on blood samples. Liquid biopsies have become extremely popular with patients as they offer a less invasive biopsy approach compared to lung punctures with a needle. This is especially valuable in late-stage trials, when tissue is often no longer available or patients are too unwell, or unwilling, to undergo another biopsy. As one of our customers once said, “Tissue is the issue”. ASPYRE helps overcome this challenge by enabling testing on peripheral blood instead of tissue.
The benefits of ASPYRE also stem from the extensive validation and optimization work that we’ve put into making it fit for clinical application. We validated the assay so that results obtained with it could be used confidently within clinical trials. That process involved verifying several aspects that are operationally critical in a clinical laboratory, including precision, accuracy, inter-run precision, intra-run precision and inter-lab precision. The latter involves repeating the same sample on different days, on different instruments, by different technicians across our global sites—an essential step in transforming a research assay into a clinical trial assay.
We also drew on our decade of experience to make the assay fit for clinical operations. Through our clinical trial experience, we know how important rapid, dependable turnaround times are when patient eligibility decisions depend on the results. The original extraction method for ASPYRE, however, was too long, which impacted the overall turnaround time for the testing. Outside of the laboratory work, testing a sample from a patient involves many other steps, such as collection at the clinical site, shipping to the testing lab, sample accessioning, and many quality control steps. During this time, the patient is waiting for the test results that determine their eligibility for a trial; they need to know as soon as possible.
…we know how important rapid, dependable turnaround times are when patient eligibility decisions depend on the results.
This is why our partners typically ask for a turnaround time of 3 to 5 days. With this in mind, we’ve optimized the ASPYRE assay to respond to fast turnaround time needs.
Alongside these operational improvements, CellCarta’s global infrastructure enables the consistent delivery of ASPYRE testing across large clinical trials. Early-phase studies typically involve smaller patient groups, but by Phase III, clinical trials expand to a global scale, with testing required in the US, Europe and China. With genomics laboratories located in each of these regions, CellCarta is well-positioned to address the needs of our customers globally and deliver consistent, high-quality testing wherever patients are enrolled.
Overall, we have elevated this assay for patient management, including providing a faster turnaround time and improving the sample processing. This, in combination with the fact that the assay is highly sensitive and circumvents the need to undergo invasive lung punctures, means ASPYRE ultimately supports both sponsors’ needs and patients’ access to clinical trials, in a more patient-centred way.
To find out more about the Aspyre® assay, download CellCarta’s validation report here >>>
The opinions expressed in this interview are those of the author and do not necessarily reflect the views of Oncology Central or Taylor & Francis Group.
No potential competing interest was reported by the contributor to this feature.
This interview was sponsored by CellCarta
