NEW YORK – Chinese cancer sequencing firm Genecast Biotechnology said this week that it plans to seek regulatory approval for its fixed-panel circulating tumor DNA minimal residual disease assay in both China and the US, having recently published what it believes is the largest study of MRD in lung cancer thus far.

While debate has flared in the US recently over the relative merits of competing companies' MRD assays using tumor-informed or tumor-agnostic approaches, Wuxi-based Genecast's method differs from both.

Launched last November in China, the test is similar to products like Natera's Signatera assays, in that it is tumor informed. But rather than using tissue-based mutation data to create small patient-specific panels, the company employs a large, fixed panel to test both tumor and blood samples.

Specific targets are selected for each patient, but this is done in silico, explained Jerry Wang, Genecast's VP for corporate development. Meanwhile, the increased available genomic real estate of the large, fixed panel means more data to mine for minute signals of residual or recurring cancer.

The rationale behind building small patient-specific panels, as Natera and other firms have done, is that it allows cost-efficient deep profiling to detect the tiny fractions of alterations that may be present in the blood of early-stage cancer patients.

Still, there are downsides to this, said Ji He, Genecast's chief information officer. "In terms of the sensitivity of the whole disease, it really depends on whether the markers are selectet correctly and whether the subclones of the tumor progression can also carry those markers." This is not a technical question, he said, but a biological issue.

"In terms of sensitivity, maybe at a particular mutation spot we may not have the higher sensitivity of a PCR, but since we cover a larger region, we actually have a higher possibility of capturing … cancer progression-related markers," he said.

Moreover, he added, it's possible to sequence more deeply with a larger panel and reach the same sensitivity of PCR. This comes with high costs, of course, but he said Genecast isn't really concerned about that, considering expectations for the cost of sequencing to continue to drop in coming years.  

Weizhi Chen, CSO of Genecast, cited timeliness as another crucial factor. "A pre-validated fixed panel gives us a lot of advantage," she said, compared to the requirements of developing and validating individual patient-specific assays. The firm's turnaround time is seven days.

Genecast's MRD launch in China last year rested on the first readout of results from a trial that investigators have now published in Clinical Cancer Research. Authors reported on the firm's MRD test performance in a cohort of more than 300 patients sampled before curative- intent surgery, immediately afterward, and one month later.

According to the authors, the data showed that a positive test result post-surgery was a strong predictor for disease relapse. MRD-positive patients who received adjuvant therapies in the trial also had improved recurrence-free survival compared to those not receiving adjuvant therapy.  

Specifically, the team reported that perioperative MRD status was associated with disease relapse with a hazard ratio of more than 11. MRD was also more predictive of relapse-free survival than other clinicopathological variables, including cancer stage.

Across the cohort, there was an 81 percent relapse rate in the MRD-positive group. This rose to 100 precent in MRD-positive patients who received no adjuvant therapy.

Wang said this week that the company's commercially available version of the test improves even further upon the assay design used in the trial, incorporating unique molecular identifiers to drive sensitivity even higher.

According to Wang, there has been a good ramp up in sales of the test in China over the last year, spurring the company to expand to additional indications in lung cancer as well as other tumor types.

Based on the data published in CCR, the company's initial launch was for single-timepoint testing, to identify patients with a signal of residual disease post-surgery, indicating a worse prognosis and potential need for adjuvant therapy.

But Wang said that Genecast now intends to expand from this to an additional monitoring version, supported by data from the same study cohort, which is currently under review for publication.

The firm is not alone, as various other companies developing ctDNA assays for early cancer have also targeted longitudinal monitoring as a clinical use case. In the US, this shift has been bolstered by Medicare Administrative Contractor Palmetto GBA's recently updated coverage guidelines for MRD assays, which include use to monitor immunotherapy response.

Chen said that the cost advantage of customized MRD panels becomes more of an issue in the monitoring context, but the company still believes the larger reach of its approach and the associated boost in sensitivity, are worth it.

Aside from pushing into the monitoring market in China, Wang said that Genecast is in discussions with China's National Medical Products Administration, with plans to seek approval for an IVD kit version of its current MRD assay.

As it moves in that direction, the company is also planning its first foray in the US cancer genomics market, with parallel plans to seek breakthrough device designation from the US Food and Drug Administration.

Wang said the company views its fixed-panel approach as a potential advantage over bespoke assays in terms of suitability for dissemination as an IVD. Although there is informatic personalization, the wet-lab aspect can be completely standardized.

Genecast also has ambitions to expand to other cancer types in the next few years, including colorectal cancer, which has been the primary focus for MRD companies in the US and for which the firm has a case-control trial awaiting publication, as well as breast, gastric, head and neck, and pancreatic cancers.