Nature Medicine Publishes Two Studies Highlighting Signatera’s Clinical Utility in Patients with Gastrointestinal Malignancies
- Results from the AMPLIFY-201 trial showed promising tumor biomarker responses in 84% of patients.
- The study utilized circulating tumor DNA (ctDNA)-positivity in conjunction with other tumor biomarkers for enrollment, highlighting the use of Signatera for detecting early evidence of anti-tumor activity of a drug candidate.
- ctDNA clearance was observed in 24% of patients, demonstrating the potential utility of ctDNA as a reliable surrogate biomarker for treatment efficacy.
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Insights
The use of circulating tumor DNA (ctDNA) as a biomarker in the evaluation of cancer vaccines represents a significant advancement in oncology. Specifically, the AMPLIFY-201 trial's focus on ctDNA to monitor treatment response to the ELI-002 vaccine offers a more sensitive and specific method of assessing tumor burden compared to traditional serum tumor antigens. The clearance of ctDNA in 24% of patients suggests a potential for the vaccine to induce a meaningful anti-tumor response. However, the clinical relevance of ctDNA clearance needs to be interpreted with caution until correlated with clinical outcomes such as survival and recurrence rates.
While the study's sample size is relatively small, the high response rate (84%) based on tumor biomarkers is promising. It is crucial to note that the trial is in phase I, primarily designed to assess safety and that efficacy conclusions are preliminary. Further studies are needed to confirm these findings and determine the optimal dosing strategy for ELI-002. The potential for ctDNA to serve as a surrogate biomarker could expedite drug development by providing early evidence of efficacy, but it should not replace long-term clinical endpoints.
The publication of the AMPLIFY-201 trial results in Nature Medicine underscores the growing interest in personalized and tumor-informed molecular residual disease (MRD) tests like Signatera. The trial's design, which integrates ctDNA analysis for patient enrollment and monitoring, is a testament to the evolving landscape of precision medicine in oncology. The ability to detect MRD with high specificity offers a potential paradigm shift in how treatment efficacy is measured and how clinical trials are conducted.
From a research perspective, the use of ctDNA as a secondary endpoint to assess biomarker response is innovative and could become a standard in future clinical trials. This approach may enable more dynamic and real-time assessment of drug efficacy, potentially reducing the time and cost associated with traditional endpoints. However, the long-term impact on clinical trial design will depend on the validation of ctDNA as a predictive biomarker for patient outcomes across various cancer types and treatment modalities.
Natera's announcement of these study results may have a positive impact on investor sentiment, given the high interest in personalized medicine and the potential market growth for MRD testing. The ability of Signatera to identify patients who could benefit from specific treatments like ELI-002 positions Natera at the forefront of this niche market. The specificity and sensitivity of Signatera could make it an industry standard for MRD testing, which would have significant implications for the company's market share and revenue growth.
However, investors should also consider the competitive landscape and the regulatory hurdles that Natera may face in bringing such a test to market. The adoption of new biomarkers often requires extensive validation and endorsement from regulatory bodies and professional societies. Additionally, the market impact will be contingent upon the outcomes of subsequent trial phases and the potential integration of Signatera into clinical practice guidelines.
AMPLIFY-201, a phase I trial evaluating treatment response to the ELI-002 vaccine, is the first study to read out using ctDNA to enroll and monitor patients with solid tumors
PANDA study shows ctDNA status in patients with gastric and gastroesophageal cancers is strongly associated with recurrence risk and pathologic response
The first study shows results from the single-arm, phase I AMPLIFY-201 trial evaluating the ELI-002 cancer vaccine. The study enrolled a total of 25 patients (20 pancreatic, 5 colorectal), 21 of whom were Signatera-positive after locoregional treatment. Signatera dynamics were also used as a secondary endpoint to assess tumor biomarker response, together with serum tumor antigens. This study is the first of its kind to have utilized circulating tumor DNA (ctDNA)-positivity in conjunction with other tumor biomarkers for enrollment, highlighting the use of Signatera for detecting early evidence of anti-tumor activity of a drug candidate to help assess for a dose response.
The study reported that tumor biomarker responses were observed in 21/25 patients (
“We are excited about our partnership with Natera, which has resulted in a successful prospective, phase I clinical trial focused on trial enrichment by enrolling Signatera-positive patients and monitoring therapy response in patients receiving a cancer vaccine,” said Christopher Haqq, MD, PhD, Elicio Therapeutic, Inc’s executive vice president, head of research and development, and chief medical officer. “We are optimistic about the potential for this study to improve outcomes for patients with pancreatic and colorectal cancer, who face clinical challenges and are often incurable when ctDNA is detected after treatment.”
A second study published in Nature Medicine, called PANDA, is a single-arm, open-label, phase II study that investigated preoperative atezolizumab plus chemotherapy in patients with resectable, non-metastatic gastric and gastroesophageal junction adenocarcinoma. The study included 20 patients who underwent surgery and were evaluated for safety, pathologic response, and survival endpoints, and Signatera was used to detect and monitor ctDNA dynamics in all 20 patients.
The PANDA study found that ctDNA clearance after neoadjuvant therapy correlated with pathologic response in 11/11 patients, while 3/6 patients with poor pathologic response remained ctDNA-positive (P=0.029). None of the patients with complete pathologic response (pCR) were ctDNA-positive, and among the nonresponders who were ctDNA negative (n=3), the study reported superior long-term outcomes. Additionally, ctDNA-positivity at the MRD and follow-up time points was associated with a recurrence rate of
“We’re pleased to see these excellent results from the PANDA study which demonstrate the strong correlation between ctDNA and pathologic response pre-surgery and the therewith associated recurrence risk, highlighting the potential utility of Signatera in gastric and gastroesophageal cancers,” said Myriam Chalabi MD, PhD, medical oncologist, Netherlands Cancer Institute, and principal investigator of the PANDA study.
“PANDA and AMPLIFY-201 add to the growing number of studies supporting the use of Signatera across various GI indications, showing the promise of tumor-informed ctDNA testing to help personalize treatment strategies,” said Alexey Aleshin, general manager of oncology and early cancer detection at Natera. “These studies also point to the valuable insights longitudinal ctDNA monitoring can provide in the evaluation of novel therapies.”
About Signatera
Signatera is a personalized, tumor-informed, molecular residual disease test for patients previously diagnosed with cancer. Custom-built for each individual, Signatera uses circulating tumor DNA to detect and quantify cancer left in the body, identify recurrence earlier than standard-of-care tools, and help optimize treatment decisions. The test is available for clinical and research use and is covered by Medicare for patients with colorectal cancer, breast cancer (stage IIb and higher) and muscle invasive bladder cancer, as well as for immunotherapy monitoring of any solid tumor. Signatera has been clinically validated across multiple cancer types and indications, with published evidence in more than 50 peer-reviewed papers.
About Natera
Natera™ is a global leader in cell-free DNA testing, dedicated to oncology, women’s health, and organ health. We aim to make personalized genetic testing and diagnostics part of the standard of care to protect health, and inform earlier, more targeted interventions that help lead to longer, healthier lives. Natera’s tests are validated by more than 180 peer-reviewed publications that demonstrate high accuracy. Natera operates ISO 13485-certified and CAP-accredited laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) in
Forward-Looking Statements
All statements other than statements of historical facts contained in this press release are forward-looking statements and are not a representation that Natera’s plans, estimates, or expectations will be achieved. These forward-looking statements represent Natera’s expectations as of the date of this press release, and Natera disclaims any obligation to update the forward-looking statements. These forward-looking statements are subject to known and unknown risks and uncertainties that may cause actual results to differ materially, including with respect to whether the results of clinical or other studies will support the use of our product offerings, the impact of results of such studies, our expectations of the reliability, accuracy and performance of our tests, or of the benefits of our tests and product offerings to patients, providers and payers. Additional risks and uncertainties are discussed in greater detail in "Risk Factors" in Natera’s recent filings on Forms 10-K and 10-Q and in other filings Natera makes with the SEC from time to time. These documents are available at www.natera.com/investors and www.sec.gov.
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Investor Relations: Mike Brophy, CFO, Natera, Inc., 510-826-2350, investor@natera.com
Media: Lesley Bogdanow, VP of Corporate Communications, Natera, Inc., pr@natera.com
Source: Natera, Inc.
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