Developing effective cancer treatments is one of the most challenging frontiers in drug development, where precision, timing, and sensitivity can dramatically influence both clinical outcomes and regulatory success. Traditional trial designs rely on imaging or pathological markers that often fail to capture the early biological response to treatment. Simsen Diagnostics’ tumour-informed ctDNA analysis offers a paradigm shift, allowing real-time, ultra-sensitive molecular monitoring of tumour dynamics. For pharmaceutical companies, it represents not just a diagnostic innovation, but a tool for designing smarter, more efficient, and more informative clinical trials.
Understanding Tumour-Informed ctDNA Analysis
Circulating tumour DNA (ctDNA) refers to small fragments of tumour-derived DNA found in a patient’s bloodstream. By detecting and quantifying these fragments, researchers can monitor disease burden and treatment efficacy through a simple blood draw.
However, not all ctDNA tests are created equal. A key distinction lies between tumour-naïve and tumour-informedapproaches:
- Tumour-naïve assays use fixed mutation panels that attempt to cover common cancer-linked genes, useful but often limited in sensitivity and specificity.
- Tumour-informed assays, like Simsen® Personal, are entirely patient-specific, leveraging each patient’s tumour genomic information to design a bespoke assay targeting unique, somatic tumour variants.
This personalized design profoundly enhances detection sensitivity (as low as 0.01% variant allele frequency, compared to 0.5% or higher for fixed panels) and drastically reduces false positives, even in the presence of confounding factors such as clonal haematopoiesis of indeterminate potential (CHIP)—a common source of noise in liquid biopsy data.
Why This Matters for Clinical Trials
Pharmaceutical companies are increasingly integrating ctDNA analysis into oncology clinical trial design, particularly in early-stage solid tumours or adjuvant therapy settings, where long timelines and large cohorts have historically slowed development. Simsen’s tumour-informed ctDNA technology creates opportunities across the entire trial continuum:
- Streamlining Patient Selection and Enrichment
ctDNA-based minimal residual disease (MRD) detection enables pharma developers to stratify or enrich their trial populations. By recruiting ctDNA-positive patients, those at higher risk of recurrence, trials gain statistical power with smaller sample sizes.
For example, colorectal cancer simulations have shown that patient enrichment using ctDNA profiling can reduce required enrolment by up to 8-fold and cut per-patient trial costs by 75%, without compromising statistical integrity. This is particularly relevant in high-cost adjuvant settings.
Simsen Personal brings unmatched adaptability to this stage; it can design assays based on whole exome sequencing (WES), whole genome sequencing (WGS), or even large tumour panels. This flexibility ensures that trials can be set up efficiently, regardless of the genomic information available at baseline.
- ctDNA as an Early Marker of Treatment Response
Changes in ctDNA levels can indicate tumour dynamics months before radiographic progression or recurrence becomes visible. Multiple studies have demonstrated this lead-time advantage, ranging from 2 to 11 months, depending on cancer type and sampling frequency.
Pharma companies can leverage Simsen’s high-sensitivity detection to:
- Determine on-target drug activity earlier.
- Evaluate the duration and depth of molecular response.
- Monitor adaptive resistance and emerging mutations as they appear.
In trials exploring immunotherapies or targeted agents, ctDNA tracking can also help distinguish pseudoprogression, hyperprogression, or exceptional responders, cases where imaging might otherwise give ambiguous results.
- Using ctDNA as a Surrogate Endpoint
Validated surrogate markers are invaluable for regulatory acceleration. Increasing evidence shows ctDNA clearance or dynamics correlate strongly with progression-free and overall survival outcomes across solid tumour types.
Simsen’s patient-tailored assays could therefore serve as early surrogate endpoints, demonstrating molecular efficacy much faster than traditional survival data allow. This offers significant advantages for interim analyses, adaptive trial designs, and potentially even accelerated drug approvals.
- Continuous, Longitudinal Monitoring
The dynamic nature of Simsen’s assay design allows persistent monitoring throughout a trial’s duration. Tumours evolve under therapeutic pressure, and fixed panels may miss new clones or resistance mutations that arise.
Simsen’s tumour-informed assays inherently adapt to the tumour’s specific mutational landscape, maintaining representativeness and reducing bias. Regular ctDNA sampling provides a real-time molecular snapshot of treatment response, residual disease, or recurrence.
With rapid turnaround times, personalized assay development in about four weeks and ctDNA test results in just 4–8 working days (fast-track option), Simsen provides actionable insights that match the pace of modern drug development.
Practical and Regulatory Advantages
- Trial Efficiency: Smaller, enriched cohorts with faster interim results.
- Regulatory Confidence: ctDNA increasingly recognised by authorities as a biomarker for early efficacy assessment and risk stratification.
- Comprehensive Reporting: Custom-tailored reports, including selected clinically relevant resistance markers, integrated into a single workflow.
- Ethical and Secure Data Handling: Fully EU-based, GDPR-compliant workflows ensure data privacy and mitigate cross-border regulatory limitations.
Conclusion
Pharmaceutical companies face rising expectations for precision, efficiency, and real-world relevance in oncology drug development. Simsen’s tumour-informed ctDNA technology directly addresses these pressures, offering unmatched sensitivity, flexibility, and clinical insight.
By integrating Simsen® Personal ctDNA analysis into cancer trials, sponsors can confidently:
- Shorten development timelines,
- Optimize patient selection,
- Track biological responses in real time, and
- Generate robust, actionable evidence for faster regulatory approval.
In short, Simsen brings molecular precision to the heart of clinical research, helping drug developers see the unseen in cancer biology and bring effective therapies to patients faster.
If you are interested in learning more or discuss your trial requirements, please reach out via our contact form.
