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NeoGenomics Eyes Bladder Cancer as Future Indication for Radar MRD Test


NEW YORK – Buoyed by new promising data, NeoGenomics is pursuing a new bladder cancer indication for its minimal residual disease test, Radar, which came under its umbrella with the acquisition of liquid biopsy firm Inivata in 2021. 

In a study published earlier this month in Nature Medicine, investigators shared results from the Phase Ib NABUCCO clinical trial, which examined high- and low-dose preoperative ipilimumab (Bristol Myers Squibb's Yervoy) plus nivolumab (BMS's Opdivo) in stage III urothelial cancer. As part of the trial, the Radar assay was used during immunotherapy treatment and immediately pre-surgery, with results compared to patient outcomes.

Authors reported that circulating tumor DNA in plasma, as detected by Radar, was associated with patient responses to treatment prior to surgery, implying that the test could be used to help inform the choice to perform or avoid cystectomy, an aggressive surgery that removes the patient's bladder.

Although the data is markedly preliminary, NeoGenomics thinks it can push forward with further validation studies and eventually pursue this as a clinical testing indication.

"What we see in this case is very similar to what we're seeing in the breast cancer side where the application of MRD in the neoadjuvant setting is becoming more and more important. And this is a perfect example where overtreatment is occurring potentially," said Vishal Sikri, president of pharma services at NeoGenomics and chief commercial officer for Inivata.

"If we can avoid that bladder surgery [or avoid full cystectomy] that helps in the overall outcomes for that patient in terms of ease of life afterwards and so on," he added.

Authors of the new NABUCCO trial report wrote that the absence of ctDNA in patients' blood plasma was highly associated with both pathological complete response — the absence of disease in surgically removed tissue — and progression-free survival. The same had been true in the study's prior Phase Ia cohort.

When investigators evaluated the combined population, they calculated that among 19 patients with a pathological complete response and an evaluable pre-surgery blood sample, all but one were ctDNA-negative. Meanwhile, among 21 non-responders, only six were ctDNA-negative pre-surgery.

The NABUCCO researchers had also explored MRD testing in urine in the trial's first cohort, but urinary ctDNA didn't show the same strong association with outcome.

NeoGenomics VP of Clinical Programs Amber Carter said that the answer to why urine testing lagged blood-based ctDNA is "we don't know."

Other data has shown that urinary ctDNA can be a good source for cancer detection, but it might depend on the assay used, or the number of molecular targets, she said. The biology of tumor cells shed into the urine may play a role, as well.

NeoGenomics had announced the results as providing evidence that Radar "can be used successfully to guide decision-making and help oncologists personalize patient care based on their risk of recurrence." But Sikri clarified that this doesn't mean physicians should be doing this in clinical practice.

"I think the intention was to say that this has the potential to be used in [this way] as we go into more and more interventional trials," Sikri said.

The path forward will be akin to what NeoGenomics has been pursuing in neoadjuvant breast cancer, he added. As in breast cancer, where there is an established practice of avoiding unnecessary treatment, bladder cancer provides a natural target for therapy de-escalation strategies.

"I think bladder is interesting because there's already a movement to spare the bladder. It's already in the guidelines. Your main strategy in muscle-invasive bladder cancer is either remove the bladder or preserve the bladder, but do so without compromising overall survival," said Carter.

"We know in some people who have the bladder removed, there's still a high risk of recurrence, so there are two things that are important for us to understand and to get better at," she added. "First, we need to know which systemic approaches improve a person's likelihood of cure where you could spare their bladder … and then second, we want to know which biomarkers are able to sort out who is higher [or] lower risk to potentially inform that better, because it is quite a morbid surgery."

Authors of the NABUCCO report concluded that assessment of ctDNA in larger studies, including later survival time points, could help to build personalized strategies to de-escalate treatment. They noted that clinical strategies could include a "wait-and-see" approach with longitudinal ctDNA monitoring in patients with an absence of ctDNA after preoperative therapy.

They cited one such study, the INDIBLADE trial, which is already ongoing, assessing the efficacy of preoperative Yervoy and Opdivo followed by chemoradiation therapy as a bladder-sparing strategy.

Carter said that for its part, NeoGenomics is considering validation efforts both in independent retrospective cohorts and in interventional trials that could "further move the needle to use Radar for bladder sparing."

Sikri estimated that it may take a few years to build up enough evidence for MRD to be applied clinically in neoadjuvant bladder cancer as it is currently in other settings, mainly adjuvant colorectal cancer.

"Because it's in the neoadjuvant setting we'll get outcome data relatively quickly, but especially for these interventional trials as we start to go through them, I think we're probably looking at a couple of years," he said.