Oncodetect® MRD Test Shows Analytical Validity, Clinical Utility at ASCO

The ability to detect minimal residual disease after definitive treatment for solid tumours holds significant implications for patient prognosis and subsequent therapeutic decisions. Current methods often lack the sensitivity or specificity required for reliable detection of circulating tumour DNA (ctDNA) at very low concentrations. This gap necessitates highly sensitive and analytically validated assays that can translate into actionable clinical insights. The Oncodetect® test aims to address this need by providing a comprehensive platform for MRD detection. The prevalence of solid tumours, such as colorectal cancer and non-small cell lung cancer, underscores the critical need for improved surveillance tools. For instance, colorectal cancer is the third most common cancer globally, with over 1.9 million new cases diagnosed annually, and lung cancer remains the leading cause of cancer-related deaths. Early and accurate detection of recurrence can significantly impact patient management and survival outcomes in these large patient populations.

Analytical Validation and Clinical Evidence

The analytical validation of the Oncodetect® test involved a multi-centre evaluation to establish its performance characteristics. The assay demonstrated a limit of detection (LoD) down to a 0.001% variant allele frequency (VAF) for single nucleotide variants (SNVs) and indels, utilizing a proprietary error-correction sequencing methodology.¹ This methodology involves deep sequencing of patient-specific tumour mutations identified from a primary tumour biopsy, followed by bioinformatic filtering to distinguish true ctDNA variants from background noise and sequencing errors. Specificity was assessed using plasma samples from healthy donors (N=200), yielding a false positive rate of 0.5%.¹ Reproducibility studies, conducted across three independent laboratories, showed an inter-laboratory coefficient of variation of less than 5% for samples with VAFs above 0.01%.¹ These analytical metrics support the test's capability to reliably detect extremely low levels of ctDNA, which is crucial for identifying MRD before macroscopic recurrence.

Clinical evidence supporting the Oncodetect® test was derived from a retrospective cohort study involving 500 patients with resected stage II/III colorectal cancer (CRC). Plasma samples were collected at baseline, post-surgery, and at 3-month intervals for 2 years. Patients with detectable MRD post-surgery (N=150) had a significantly higher risk of recurrence compared to those with undetectable MRD (N=350). The hazard ratio (HR) for recurrence in the MRD-positive group was 3.8 (95% CI: 2.9-4.9; p < 0.001).² Furthermore, among patients who received adjuvant chemotherapy, those who converted from MRD-positive to MRD-negative status post-treatment demonstrated a 2-year disease-free survival (DFS) rate of 78%, compared to 45% for those who remained MRD-positive (p < 0.001).² This suggests a potential role for the Oncodetect® test in guiding adjuvant therapy decisions and monitoring treatment response, potentially allowing for tailored treatment intensification or de-escalation.

A separate prospective, observational study in non-small cell lung cancer (NSCLC) patients (N=120) undergoing curative-intent surgery also utilized the Oncodetect® test. Post-operative MRD detection was associated with a 3-fold increased risk of recurrence (HR: 3.1, 95% CI: 2.1-4.6; p = 0.002) at 18 months.³ The median time to recurrence was 9 months in MRD-positive patients versus not reached in MRD-negative patients.³ These data collectively indicate the prognostic value of the Oncodetect® test across different solid tumour types. The patient populations in both studies represent common clinical scenarios where MRD detection could provide valuable prognostic and predictive information.

Limitations of the current data include the retrospective nature of the CRC cohort, which introduces potential biases such as selection bias and confounding factors that may not have been fully accounted for. The NSCLC study, while prospective, was observational and not powered to evaluate treatment efficacy based on MRD status, thus precluding definitive conclusions about treatment modification. Further validation in larger, prospective, randomized controlled trials is necessary to definitively establish the utility of MRD-guided treatment de-escalation or escalation strategies, particularly in demonstrating improved patient outcomes. The generalizability of these findings to other tumour types and earlier disease stages also requires additional investigation, as the current studies focused on resected stage II/III CRC and NSCLC. The specific tumour-agnostic or tumour-specific panel design of the Oncodetect® test was not fully detailed, which could impact its broad applicability and the number of mutations tracked per patient. Additionally, the impact of tumour heterogeneity on MRD detection sensitivity and the potential for clonal evolution to render initial tumour-specific markers less effective over time warrant further exploration.