Pharmaceutical and Precision Medicine Companies Join Forces in the Evolving Solid Tumor MRD Detection Market

MRD (Minimal Residual Disease) refers to the presence of trace amounts of tumor cells remaining in the body after treatment for malignant tumors, serving as the root cause of cancer recurrence. Accurate MRD detection forms the foundation of personalized precision medicine for patients, enabling prediction of clinical outcomes, risk stratification, guidance of therapeutic decisions, early prediction of tumor relapse, and determination of the optimal timing for bone marrow or stem cell transplantation.

In the past two years, interest in the MRD detection sector has surged, particularly in hematologic malignancies, where products have already received regulatory approval. In 2018, Adaptive Biotechnologies’ ClonoSEQ was approved by the FDA for MRD testing in hematologic cancers. In March 2021, PanGene’s NEO-MRD, a blood cancer MRD detection product, obtained CE marking in the European Union.

Compared with MRD testing for hematologic malignancies, MRD testing for solid tumors is at an earlier stage of development and has lagged slightly in commercialization. However, the patient population with solid tumors is substantially larger than that with hematologic malignancies. According to the latest 2020 global cancer burden data released by the International Agency for Research on Cancer (IARC) of the World Health Organization, the ten most prevalent cancers worldwide are all solid tumors, affecting a cumulative total of 12.16 million patients. Therefore, there is naturally greater demand for MRD testing products among patients with solid tumors.From a long-term perspective, the market for MRD testing in solid tumors holds greater potential.

Although MRD testing for solid tumors started later, its clinical value is no less than that for hematologic malignancies. Studies have demonstrated the feasibility of using MRD testing to evaluate clinical treatment regimens and monitor prognosis in solid tumors such as lung cancer, colorectal cancer, breast cancer, and pancreatic cancer.

In November 2021, *Nature Communications*, a subsidiary journal of *Nature*, published findings from a study on ctDNA-MRD. The results demonstrated that postoperative ctDNA-MRD analysis in non-small cell lung cancer (NSCLC) not only serves a prognostic function by predicting recurrence—detecting relapse a median of 88 days earlier than imaging—but also has predictive value for assessing the benefits of adjuvant chemotherapy (with positive patients benefiting from adjuvant therapy and negative patients deriving no benefit). These findings indicate that ctDNA-MRD testing can better predict the risk of disease recurrence and help guide decision-making regarding adjuvant chemotherapy.

Guardant Health is a representative company in the field of solid tumor MRD testing, having robustly validated the clinical significance of such testing. Its approaches to R&D and commercialization also serve as a reference for Chinese enterprises.

In February 2021, Guardant Health officially launched Guardant Reveal, a solid tumor minimal residual disease (MRD) detection product for long-term recurrence monitoring in postoperative colorectal cancer patients, and obtained approval from the New York State Department of Health’s Clinical Laboratory Evaluation Program two months later.

Guardant Reveal utilizes ctDNA mutations and ctDNA methylation for MRD detection, employing a tumor-agnostic approach with a fixed panel via blood testing.

Earlier, in a retrospective study of patients with colorectal cancer, Guardant Health collected and analyzed blood samples immediately after surgical resection. The study found that 48% of patients showed signs of cancer recurrence. All cancer patients in whom residual disease was detected experienced recurrence within 18 months, with no false positives. This testing approach, combined with differentiated treatment strategies, holds promise for improving patients’ progression-free survival. In April 2021, Clinical Cancer Research published the research data for Guardant Reveal, reporting that its MRD (minimal residual disease) product achieved a sensitivity of 91% and a specificity of 100%.

Guardant Health is at the forefront of global MRD detection for solid tumors, however, in the field of MRD detection for solid tumors, the gap between overseas and domestic markets is not significant.Currently, numerous companies in China are establishing their presence in the field of solid tumor minimal residual disease (MRD) testing, including BGI Genomics, Genetron Holdings Limited, Burning Rock Biotech, Geneseeq Technology, GenePlus-Beijing, TreeO Genetics, ZhiBen Medical, 3D Medicines, and Zenith & Co. However, no products have yet received regulatory approval, indicating that opportunities in China’s solid tumor MRD testing sector are emerging.

A preliminary consensus has been reached within the industry regarding the technical modalities and detection dimensions for minimal residual disease (MRD) testing in solid tumors. In terms of technical modalities, next-generation sequencing (NGS) outperforms flow cytometry in efficiency, accuracy, and sensitivity, with multiple guidelines recommending NGS as the preferred method for MRD detection. Regarding detection dimensions, reliance solely on ctDNA mutations offers limited sensitivity, whereas the integration of ctDNA methylation and mutation analysis is widely recognized.

andIn the field of diagnostic pathways, opinions within the industry vary, and companies have adopted diverse strategic approaches.For example, Guardant Health has developed a fixed-panel MRD testing solution, while Natera, another leading U.S. company in solid tumor MRD testing, has focused on personalized, customized MRD testing solutions.

The commercial prospects for MRD detection in solid tumors are unquestionable, yet the field faces higher technical barriers, imposing stringent requirements on sensitivity, cost, turnaround time, and operational ease.For example, each patient with a solid tumor harbors only a very small number of identical gene mutations, which means that panel design is more challenging than for hematologic malignancies. The amount of ctDNA released into the peripheral blood by early-stage solid tumors is extremely low, reaching levels as low as one in ten thousand, thus requiring ultra-high sensitivity.

Thus, MRD testing for solid tumors was born.Tumor-informed (based on tumor tissue sequencing) ctDNA personalized customization solution, andTumor-agnostic (plasma-based) fixed panelThese two major testing pathways are currently both in the exploratory stage.

Fixed-panel MRD testing selects high-frequency genes to form a small panel. Using a fixed panel to meet all solid tumor MRD testing needs is the most ideal scenario. However, in reality,Cancer exhibits heterogeneity; different cancer types release distinct ctDNA profiles and mutation variants. Fixed-panel assays have limited sensitivity for detecting mutations, making it difficult to comprehensively cover all cancer patients.

Personalized Custom MRD TestingWhole-exome sequencing of tumor tissues is performed to generate a personalized genomic mutation profile for each patient, which is then incorporated into minimal residual disease (MRD) detection; customized primers are used to conduct parallel multi-mutation analysis on cell-free DNA (cfDNA).is currently the most accurate MRD detection pathway for solid tumors.However, personalized testing protocols are costly, involve lengthy workflows, and rely on tumor tissue.

It is still a distant goal to achieve disruptive innovation through substantial technical optimization of personalized testing solutions. According to Hu Yunfu, Chief Medical Officer of Genetron Holdings Limited, at present,Combining personalized custom testing with fixed panels, first using fixed-panel MRD testing for the vast majority of patients, and conducting personalized custom MRD testing for the small subset of patients not covered by fixed panels, thereby leveraging complementary advantages, represents a more accessible solution.

Overall, it is a trend for companies in the solid tumor MRD sector to simultaneously deploy both personalized custom MRD assays and fixed-panel MRD tests.

The clinical application potential of tumor NGS technology is continuously expanding, with companies specializing in precision oncology diagnostics shifting from traditional companion diagnostics toward the early screening and MRD markets, which offer greater growth opportunities.

VCBeat has noted that Genetron Holdings Limited has established extensive operations in both early cancer screening and minimal residual disease (MRD) detection. Specifically, in the field of hematologic malignancy MRD testing, Genetron entered into an exclusive licensing agreement with Hangzhou Amoun, securing global exclusive rights to the latter’s Seq-MRD® product for hematologic tumor MRD detection. Genetron subsequently launched a comprehensively upgraded version of Seq-MRD® as a laboratory-developed test (LDT).

Recently,Genetron Enters the Solid Tumor MRD Testing Arena, Announces Collaboration Agreement with AstraZeneca’s Global R&D China Center (hereinafter referred to as “AstraZeneca”) to Jointly Invest in and Develop Solid Tumor MRD Products

There are two key factors in the development of MRD detection technologies for solid tumors: technical capability and sample capability.The combination of superior technical capabilities and robust sample handling capacity is central to ensuring product performance and accelerating R&D speed.

This collaboration project is based on Genetron’s proprietary technologyMutation CapsuleAs a support, Mutation Capsule technology can perform up to 10 tests on samples without affecting sensitivity.Leveraging the reusability of samples can accelerate experimental processes and shorten R&D cycles.

Meanwhile,Mutation Capsule technology can capture and analyze gene mutation and methylation variation signals from the same sample, enabling more effective monitoring of tumor recurrence.Furthermore, a variety of other mutation types can be detected within the same library, enabling the analysis not only of different types of biomarkers but also of diverse variant forms of these biomarkers, thereby enhancing the sensitivity of minimal residual disease (MRD) detection.

When it comes to sample processing capabilities, large pharmaceutical companies have the upper hand. For these companies, MRD detection products can be applied in the clinical treatment of solid tumors for patient screening and monitoring, thereby accelerating new drug development. Therefore,Pharmaceutical companies are also eager to engage in MRD R&D, achieving win-win outcomes with precision diagnostics firms.

Globally, collaboration between precision diagnostics companies and pharmaceutical firms has become a key model for the development of minimal residual disease (MRD) detection products. Grail has entered into MRD assay development agreements with three global pharmaceutical companies—Amgen, AstraZeneca, and Bristol Myers Squibb (BMS)—to detect MRD in early-stage cancer patients using blood-based ctDNA methylation technology, thereby gaining access to extensive clinical sample data and sharing R&D costs. Additionally, GlaxoSmithKline has partnered with Adaptive Biotechnologies to use clonoSEQ in clinical trials for hematologic malignancies.

For Genetron Holdings Limited,AstraZeneca possesses a large collection of clinical samples tested using the gold-standard assay, enabling definitive determination of whether each patient has experienced recurrence after long-term follow-up.In this way, MRD products can be validated using large-scale sample data; the larger the sample size, the more accurate the determined threshold will be. Ultimately, this approach accelerates product development while enabling performance optimization.

Personalized testing protocols and fixed panels should be complementary. Hu Yunfu, Chief Medical Officer of Genetron Holdings Limited, revealed that in addition to personalized solutions, Genetron is also leveraging the unique capability of its Mutation Capsule technology to support the simultaneous detection of different types of variants.Develop a fixed-panel MRD detection assay.

AstraZeneca, which has long prioritized the Chinese market, has chosen to partner with Genetron Holdings in the cutting-edge field of MRD testing in China. This move underscores the broad prospects of precision medicine in China and sends a positive signal to the domestic sector for MRD testing in solid tumors.

MRD testing and early cancer screening are both emerging fields that hold significant importance for improving patients’ long-term survival rates and reducing healthcare costs. Early cancer screening has become a highly sought-after “golden track” in the field of oncology genetic testing, attracting substantial attention. With its immense potential, the market explosion of MRD testing is only a matter of time.

Going forward, it is essential to simultaneously strengthen market education to raise awareness of the importance of MRD testing and accelerate the domestic adoption of MRD testing products, thereby enabling more cancer survivors to benefit.

As the value and significance of MRD testing gain widespread recognition, collaborations between precision diagnostics companies and pharmaceutical firms on MRD testing products will become increasingly common.Genetron Holdings Limited is also expected to deepen its collaboration with AstraZeneca in the MRD space for solid tumors.

According to Hu Yunfu, “This collaborative project is currently in the R&D phase and marks a significant beginning for both parties’ cooperation in the field of MRD detection for solid tumors.”In the future, there is still potential for collaboration between the two parties in IVD registration and distribution channels.”

As the domestic MRD testing sector gradually matures, intensified competition—akin to that seen in companion diagnostics and early screening—is inevitable. However, high-quality products remain a scarce resource in the market. A company’s path to success will lie in its comprehensive capabilities, including broad coverage, deep strategic deployment, and robust technical and clinical validation.