Personalis Showcases Advanced ctDNA Monitoring & Therapy Resistance Insights at AACR 2026
Personalis, has unveiled a series of compelling clinical findings and technological advancements at the American Association for Cancer Research Annual Meeting 2026, highlighting the growing clinical value of its ultrasensitive circulating tumor DNA (ctDNA) platform, NeXT Personal®. The presentations—comprising one oral podium session and three poster discussions—collectively emphasize how highly sensitive molecular monitoring can transform cancer care by enabling earlier intervention, more precise treatment decisions, and improved tracking of therapy resistance.
At the core of these presentations is the expanding role of ctDNA in oncology, particularly for monitoring treatment response, detecting minimal residual disease (MRD), and identifying early signs of relapse. By leveraging its NeXT Personal assay, Personalis demonstrated how ultrasensitive detection can uncover molecular changes that are often missed by conventional diagnostic methods, thereby offering clinicians deeper insights into disease progression and therapeutic effectiveness.
One of the most significant highlights came from the NEOPRISM-CRC trial, which focused on patients with high-risk stage II–III dMMR/MSI-H colorectal cancer. This study was presented during a podium session by Dr. Jiang from University College London and explored the use of NeXT Personal in monitoring patients undergoing neoadjuvant therapy with pembrolizumab. Neoadjuvant therapy, administered before surgical intervention, is increasingly used to shrink tumors and improve surgical outcomes, but assessing its effectiveness in real time has remained a challenge.
The study demonstrated that NeXT Personal achieved 100% sensitivity in detecting disease at baseline, underscoring its robustness as a diagnostic tool. More importantly, researchers identified three distinct molecular response patterns among patients: super molecular responders, dynamic molecular responders, and poor molecular responders. These categories were based on how quickly and effectively ctDNA levels declined during treatment.
Patients classified as super molecular responders showed rapid clearance of ctDNA by the second cycle of therapy. Remarkably, all patients in this group achieved a pathological complete response (pCR), meaning no detectable cancer remained at the tissue level following treatment. This strong correlation suggests that early ctDNA clearance could serve as a powerful predictor of treatment success. On the other end of the spectrum, poor molecular responders—those whose ctDNA levels remained relatively unchanged—did not achieve pCR, indicating resistance to therapy.
This ability to stratify patients based on molecular response offers a crucial clinical advantage. It provides physicians with an early window to modify treatment strategies before surgery, potentially improving outcomes for patients who are not responding optimally. Following surgery, the test further demonstrated exceptional performance, achieving 100% negative predictive value and 100% specificity in predicting disease relapse. These findings reinforce the reliability of ctDNA as a post-treatment surveillance tool.
Beyond controlled clinical trials, Personalis also presented large-scale real-world evidence supporting the ultrasensitive performance of NeXT Personal. In an analysis of nearly 25,000 plasma samples collected from 10,000 patients across diverse clinical settings, the assay consistently demonstrated a median limit of detection of just 1.92 parts per million (PPM). This level of sensitivity is particularly significant because it enables detection of extremely low levels of tumor DNA that would otherwise go unnoticed.
The real-world data revealed that 39% of MRD-positive detections occurred at levels below 100 PPM, with 14.6% falling below 10 PPM. These findings highlight the importance of ultrasensitive assays, as a substantial proportion of clinically relevant signals exist at very low concentrations. Missing these signals could delay diagnosis of recurrence or lead to incomplete assessment of treatment response.
Importantly, the dataset encompassed more than 14 cancer types, spanning stages I through IV, and included a wide range of sample conditions. This diversity demonstrates that NeXT Personal maintains high performance across varied clinical scenarios, further validating its utility in routine oncology practice.
In addition to its sensitivity, Personalis introduced a new innovation designed to address one of the most challenging aspects of cancer treatment: therapy resistance. The company debuted the Real-Time Variant Tracker™, an opt-in feature integrated into the NeXT Personal MRD platform. This tool enables simultaneous monitoring of MRD while tracking specific genetic mutations associated with resistance to therapy.
For example, mutations such as ESR1 mutation—commonly linked to resistance in certain cancers—can be identified and followed over time. The feature demonstrated a specificity exceeding 99.9%, ensuring that detected mutations are highly reliable. In the real-world cohort, resistance-associated mutations were identified in 38% of MRD-positive patients, providing clinicians with actionable insights into how tumors evolve under therapeutic pressure.
This capability represents a major step forward in precision oncology. Rather than reacting to clinical relapse after it occurs, physicians can proactively monitor the emergence of resistance and adjust treatment strategies accordingly. This dynamic approach to cancer management has the potential to extend treatment effectiveness and improve patient outcomes.
Another important study presented at AACR 2026 was the DARWIN 2 trial, which focused on patients with metastatic non-small cell lung cancer receiving immunotherapy. The results demonstrated the power of ctDNA monitoring in predicting long-term outcomes. Patients who achieved a durable molecular complete response (dmCR)—defined as sustained clearance of ctDNA—remained 100% progression-free at three years. In contrast, patients who did not achieve molecular clearance were five times more likely to experience disease progression.
These findings underscore the prognostic value of ctDNA in immunotherapy settings, where traditional imaging may not fully capture treatment response. By providing a molecular-level view of disease activity, NeXT Personal enables more accurate risk stratification and supports more informed clinical decision-making.
Taken together, the data presented by Personalis at AACR 2026 illustrate a comprehensive vision for the future of cancer care—one in which ultrasensitive molecular diagnostics guide every stage of the patient journey. From initial diagnosis and treatment selection to monitoring response, detecting recurrence, and tracking resistance, ctDNA-based approaches are poised to become an integral part of precision oncology.
The company’s advancements highlight not only technological innovation but also a broader shift toward personalized medicine. By tailoring treatment strategies based on real-time molecular insights, clinicians can move beyond one-size-fits-all approaches and deliver more targeted, effective care.
As the field continues to evolve, the integration of tools like NeXT Personal and Real-Time Variant Tracker™ into clinical workflows could redefine standards of care. The ability to detect cancer earlier, monitor it more precisely, and respond to changes more rapidly represents a significant leap forward in improving outcomes for patients across a wide range of cancer types.
In summary, Personalis’ presentations at AACR 2026 demonstrate the transformative potential of ultrasensitive ctDNA monitoring. Through rigorous clinical validation, expansive real-world data, and innovative features for resistance tracking, the company is advancing the role of molecular diagnostics in oncology. These developments not only enhance our understanding of cancer biology but also bring us closer to a future where cancer management is truly personalized, proactive, and precise.
About Personalis, Inc.
At Personalis, we are transforming the active management of cancer through breakthrough personalized testing. We aim to drive a new paradigm for cancer management, guiding care throughout the patient journey. Our highly sensitive assays combine tumor-and-normal profiling with proprietary algorithms to deliver advanced insights even as cancer evolves over time. Our products are designed to detect minimal residual disease (MRD) and recurrence at the earliest timepoints, enable selection of targeted therapies based on ultra-comprehensive genomic profiling, and enhance biomarker strategy for drug development. Personalis is based in Fremont, California.
