Genecast Advances Solid Tumor MRD Detection with Large-Scale Prospective Studies and NGS Innovation

Following companion diagnostics and early screening, minimal residual disease (MRD) has emerged as a promising new frontier in the field of precision oncology diagnostics, serving as a critical driver for the rapid iteration and advancement of cancer diagnosis and treatment technologies.

MRD refers to minimal residual disease. After treatment for malignant tumors, trace amounts of tumor cells may remain in the body, serving as the root cause of tumor recurrence. Dynamic MRD monitoring helps patients determine whether detectable residual tumor cells persist after curative surgery or therapy, enabling early detection of signs of cancer recurrence. Currently, ctDNA is the most prominent method for MRD detection.

According to a report by LeadLeo Research Institute, the market size of dynamic MRD monitoring in China was approximately RMB 540 million in 2020, measured by terminal sales. The overall market is projected to reach RMB 9.68 billion in 2021 and is expected to grow to around RMB 91.97 billion by 2025, indicating broad market prospects.

Globally, MRD testing was first implemented in the field of hematologic malignancies, where the market for MRD assessment is relatively mature. Adaptive Biotechnologies’ hematologic malignancy testing product, ClonoSEQ, received FDA approval in 2018. ClonoSEQ has generated substantial commercial value for Adaptive. According to Adaptive’s annual report, the company performed more than 22,500 ClonoSEQ tests in 2021, representing a 48% increase from 2020, and pharmaceutical companies paid $10 million in milestone payments for collaborations involving ClonoSEQ.

The solid tumor MRD sector started later but offers a larger market opportunity. Among the cancers with high incidence and mortality rates in China, the leading types—lung cancer, breast cancer, colorectal cancer, and liver cancer—are all solid tumors. However, at this stage, MRD testing for solid tumors faces greater challenges than hematologic malignancies in terms of technology and clinical implementation, and the industry as a whole remains in its early stages.

To accelerate the development of the MRD sector for solid tumors, Genecast and the Chinese Society of Clinical Oncology (CSCO) jointly hosted the “CSCO-Genecast Summit on Precision Therapy” on May 14. The summit focused on advances in MRD testing within the context of precision oncology trends and explored the potential for MRD testing to play a greater role throughout the entire cancer care continuum.

At the forum, Genecast unveiled its comprehensive portfolio of solid tumor MRD products, showcasing its leading position in the solid tumor MRD sector.

MRD testing is valuable in a variety of solid tumors, including colorectal cancer, lung cancer, breast cancer, bladder cancer, and esophageal cancer.

Currently, companies with a global footprint in the solid tumor MRD sector include Guardant Health, Natera, and ArcherDX. In April 2021, Guardant Health’s colorectal cancer MRD testing product, Guardant Reveal, received approval from the New York State Department of Health’s Clinical Laboratory Evaluation Program (CLEP). Natera’s solid tumor MRD products have been utilized in numerous clinical studies across multiple cancer types, including non-small cell lung cancer, bladder cancer, breast cancer, and colorectal cancer. ArcherDX focuses on lung cancer.

From the perspective of the current global market status, colorectal cancer MRD testing has advanced more rapidly; however, leading overseas companies in solid tumor MRD detection exhibit distinct differences in their cancer type portfolios, with limited overlap.

Regarding the strategic layout for MRD testing across solid tumor types, Du Bo, founder of Genecast, stated: “When selecting cancer types for strategic deployment, we primarily consider two factors: first, the size of the patient population likely to benefit from MRD testing; and second, whether there are numerous clinically available treatment options for that cancer type.“Through the conduct of relevant clinical studies, the relationship between test results and the selection of treatment regimens has been elucidated, demonstrating that MRD testing can effectively differentiate and assess the risk of postoperative recurrence across various tumor stages, thereby assisting clinicians in selecting subsequent treatment plans that maximize patient benefit.”

From the perspectives of the number of beneficiaries and treatment modality selection,Genecast was the first to establish a presence in MRD testing for lung cancer.

Lung cancer is the leading cancer in China. According to the latest 2020 global cancer burden data released by the International Agency for Research on Cancer (IARC) of the World Health Organization, there were 815,600 new cases and 710,000 deaths from lung cancer in China in 2020, ranking first in both incidence and mortality rates.

For early-stage lung cancer, despite surgical resection, some patients still experience postoperative disease recurrence or metastasis. MRD detection can predict recurrence before imaging methods and before the onset of clinical symptoms in patients. If the test is positive, early intervention can be initiated to select appropriate treatment options as soon as possible, helping to improve patient survival benefits.

Therefore,Lung cancer exhibits a strong reliance on MRD testing, necessitating the use of test results to select the most appropriate treatment strategy.

The necessity and urgency of MRD testing in lung cancer have gained clinical recognition. In 2021, the “Consensus on the Detection and Clinical Application of MRD in Lung Cancer” was reached at the 18th China Lung Cancer Summit Forum.

In fact, as early as November 2020, Genecast launched its MRD detection product for early- to mid-stage non-small cell lung cancer based on its self-developed MinerVa platform—Langweibo™, using ctDNA as a biomarker, it features ultra-high sensitivity and exceptional specificity, with a limit of detection (LOD) as low as 0.007%. It can track varying numbers of mutations, while maintaining a stable specificity of 99.5%–99.9%, thereby meeting clinical needs for prognostic assessment, recurrence monitoring, and treatment response monitoring, and assisting clinicians in making therapeutic decisions.

The same applies to colorectal cancer: the potential beneficiary population for MRD testing is large, and treatment decisions are closely tied to MRD test results. In 2021, ctDNA-based MRD assessment was incorporated into the NCCN Guidelines for Colon Cancer.

For colorectal cancer, Genecast has launched an MRD detection product for patients with Stage I–III colorectal cancer after radical surgery—Changweibo™, enabling comprehensive tracking of hotspot genes in tumor tissues, as well as monitoring second primary tumors and tumor evolution information. The limit of detection is as low as 0.007%, with a specificity of 99.5%–99.9%, demonstrating high sensitivity and specificity.

Du Bo revealed that Genecast will subsequently launch pan-cancer MRD detection products, achieving comprehensive coverage of major solid tumors.

From the perspective of clinical application, MRD testing for solid tumors is still in its early stages and has not been widely adopted. Du Bo stated, “To further advance the clinical implementation of minimal residual disease (MRD) detection in solid tumors, it is essential to continuously innovate technologically while concurrently generating robust clinical trial data to validate its clinical utility.”

In terms of technological innovation, the residual level of circulating tumor cells in the blood of early-stage patients after surgery is extremely low, imposing stringent requirements on background noise, sensitivity, and specificity, thereby creating a very high technical barrier. Furthermore, since different tumors release distinct mutations, there is significant variability in MRD detection across different solid tumors, which further increases the technical difficulty.

Genecast’s MRD detection products for lung cancer and colorectal cancer are both developed based on the MinerVa platform.The MinerVa platform utilizes a 769-gene panel (product: Baishibo^®), it can comprehensively cover various mutation types, including driver mutations, clonal mutations, and passenger mutations. By employing a panel design with differential weighting, it doubles the sequencing depth for hotspot regions in lung and colorectal cancers (≥30,000X), thereby ensuring the sensitivity of MRD detection.

In terms of specificity, Genecast’s Big Data Center maintains a large-sample baseline noise library of negative plasma. By modeling multi-dimensional noise features along locus and fragment axes and employing joint confidence probability analysis for multiple variants, it ensures the specificity of MRD detection.

In terms of clinical evidence, unlike driver gene testing, MRD detection in solid tumors requires long-term dynamic follow-up and the collection of high-quality clinical data to robustly demonstrate its clinical value.

Building on the technological development and validation of the MinerVa platform, Genecast has collaborated with West China Hospital of Sichuan University to launch LUNGCA, a large-scale, multicenter, prospective study on molecular prognostic markers for lung cancer. This is, to date,The World’s Largest MRD Cohort Study in Lung Cancer, filling the gap in large-sample, multicenter, prospective study data for non-small cell lung cancer.

The LUNGCA cohort enrolled a total of over 400 patients, with 67.0% at stage I and 84.8% diagnosed with lung adenocarcinoma, consistent with the distribution of real-world lung cancer surgical patients. Furthermore, the LUNGCA cohort conducted long-term follow-up, with a median follow-up time of 1,068 days.

Data show that the recurrence rate within one month postoperatively was 80.8% in patients with ctDNA-MRD positivity, significantly higher than the 16.2% observed in those with negativity, indicating that postoperative ctDNA-MRD status is a significant predictor of recurrence in postoperative patients. The results from the LUNGCA cohort study validated that ctDNA within one month after surgery can serve as a biomarker for predicting recurrence and detecting MRD.

In recent years, continuous innovations in MRD detection technology, the successive disclosure of clinical trial data for cancers such as lung cancer and colorectal cancer, and active collaborations between pharmaceutical companies and precision diagnostics firms to conduct drug clinical trials based on MRD products have all strongly promoted the clinical adoption of MRD testing, leading to a rapid increase in clinical awareness of MRD detection.

Genecast CSO Chen Weizhi believes: “The greater challenge ahead lies not in R&D, but in clinical translation.“Companies should not only focus on refining MRD technology for solid tumors but also consider how to effectively apply it to the dynamic monitoring and clinical treatment management of patients with solid tumors, thereby providing physicians with valuable insights from solid tumor MRD testing and ultimately benefiting patients.”

CurrentlyMRD in solid tumors also faces significant challenges at the regulatory level.Unlike the well-established use of genetic testing to guide targeted therapy, MRD detection in solid tumors lacks clearly defined loci, making comprehensive technical validation challenging. MRD tracking focuses on each patient’s personalized tumor mutation profile. “In this context, companies need to conduct more thorough, robust, and comprehensive technical validations while maintaining close communication with regulatory authorities. They should align with advancements in the field and clinical needs, jointly explore challenges and solutions in the standardization and normalization of precision monitoring products for early-stage cancer, and collectively promote the standardized development of the industry,” said Chen Weizhi.

Overall, MRD testing for solid tumors is undoubtedly an emerging trend in precision oncology diagnostics; however, there is still a long way to go. Extensive technical and clinical validation is required, with large-scale prospective clinical studies serving as the cornerstone for gaining clinicians’ trust in MRD testing products. Moving forward, companies must make dual efforts in technological innovation and clinical research to benefit more cancer patients.