Natera Announces DECIPHER: A Phase II, Single-Arm Adjuvant Trial in Gastroesophageal Cancer
Natera (NASDAQ: NTRA) has launched DECIPHER, a Phase II, single-arm trial using its Signatera™ test to guide treatment in gastroesophageal cancer patients. This study, the first to evaluate the HER2-directed antibody-drug conjugate for such patients, aims to enroll 25 participants from over 10 UK sites. Patients showing molecular residual disease (MRD) positivity after neoadjuvant chemotherapy and surgery will receive investigational therapy for up to eight cycles instead of the standard adjuvant chemotherapy. Signatera will monitor MRD clearance, the primary endpoint. Previous data showed high disease progression risk for Signatera-positive patients post-standard treatment. DECIPHER aims to offer these patients a better chance at cure.
- Launch of DECIPHER trial, a first-of-its-kind study in gastroesophageal cancer using Signatera.
- 25 patients to be enrolled from over 10 sites in the UK.
- Aim to demonstrate improved outcomes by pairing Signatera with innovative therapies.
- Previous data showed high disease progression risk and zero 24-month overall survival rate for Signatera-positive patients post-standard treatment.
Insights
The DECIPHER trial marks a significant milestone in the treatment of gastroesophageal adenocarcinoma (EGC), a cancer type with historically poor survival rates. The study's focus on using Signatera to guide patient selection and assess the efficacy of a novel HER2-directed adjuvant treatment is noteworthy for several reasons.
Firstly, Signatera's use as a biomarker to measure molecular residual disease (MRD) can potentially revolutionize how treatment efficacy is assessed in real-time, allowing for a more personalized treatment approach. The high sensitivity of Signatera in detecting MRD across various cancer types, including EGC, provides a robust method to identify patients who might benefit the most from the investigational therapy.
Secondly, the decision to forgo standard-of-care adjuvant chemotherapy for Signatera-positive patients in favor of the HER2-directed antibody-drug conjugate could lead to better outcomes if the trial is successful. This approach aligns with the growing trend in oncology toward personalized, biomarker-driven therapies, which aim to reduce unnecessary treatments and focus on targeted interventions.
The trial's design also addresses a critical gap highlighted by the PLAGAST study, which showed that patients who were Signatera-positive post-neoadjuvant chemotherapy and surgery had a zero 24-month overall survival rate despite standard treatments. This underscores the urgent need for more effective adjuvant therapies, particularly for those at high risk of disease progression.
In summary, the DECIPHER trial's innovative approach and potential to improve outcomes for EGC patients make it a pivotal study to watch in the oncology field. This trial could pave the way for new treatment paradigms in gastroesophageal cancer.
The DECIPHER trial is an exciting development in the field of gastroesophageal cancer treatment. The trial's use of a novel HER2-directed antibody-drug conjugate for patients who are Signatera-positive after neoadjuvant chemotherapy and surgery is particularly significant. This is the first time such a treatment is being evaluated in this specific patient population and it addresses a critical need for more effective adjuvant therapies.
One of the key aspects of this trial is the reliance on Signatera to measure MRD. This personalized, tumor-informed approach allows for a more precise assessment of treatment efficacy, potentially leading to better patient outcomes. By monitoring MRD clearance as the primary endpoint, the trial aims to provide a clear indication of the investigational therapy's effectiveness in eliminating residual disease.
Moreover, the trial's adaptive design offers a unique opportunity for patients who have not responded to standard therapies. By using a biomarker-driven approach, the study is designed to identify those most likely to benefit from the investigational therapy, thereby maximizing the potential for a cure.
The inclusion of patients from multiple sites across the United Kingdom ensures a diverse patient population, which is important for the generalizability of the trial's findings. If successful, this trial could lead to a paradigm shift in the treatment of gastroesophageal cancer, offering new hope to patients with this challenging disease.
First-of-its-kind study in gastroesophageal adenocarcinoma using Signatera to guide treatment and assess the efficacy of a novel HER2-directed adjuvant treatment
DECIPHER (Developing ctDNA Guided Adjuvant Therapy for Gastroesophageal Cancer) is a single-arm, open-label phase II trial, and the first trial to evaluate the efficacy of a HER2-directed antibody-drug conjugate in gastroesophageal adenocarcinoma (EGC) patients in the adjuvant setting. The study plans to enroll 25 patients from more than 10 sites across the
“With an adaptive approach aimed at eliminating MRD, DECIPHER is designed to offer patients a second chance at a cure when they have not responded to standard of care therapies,” said Dr. Elizabeth Smyth, M.D., consultant in medical oncology at Oxford University Hospitals NHS Foundation Trust l and chief investigator of the trial. “Signatera’s personalized, tumor-informed approach, which has demonstrated high sensitivity across several different cancer types including EGC, will be a key component of this study.”
This launch of DECIPHER follows data from the PLAGAST study presented last month at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. The data showed that EGC patients who were Signatera-positive following neoadjuvant FLOT (fluorouracil, leucovorin, oxaliplatin and docetaxel) chemotherapy and surgical resection were at an extremely high risk of disease progression by 12 months, despite standard of care adjuvant treatment, and had a 24-month overall survival rate of zero.1
Gastroesophageal cancer is a common global cancer that has sustained a nearly 2.5-fold increase in incidence over the last two decades.1 Patients with early-stage disease are typically treated with neoadjuvant chemotherapy, followed by surgery and adjuvant chemotherapy. Despite this aggressive and multimodal approach, treatment is curative in less than 50 percent of patients.2
“We are pleased to work with leading investigators in the
DECIPHER will be featured today, June 27, 2024, in a poster at the European Society for Medical Oncology Gastrointestinal Cancers (ESMO GI) Congress 2024 in
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, ovarian cancer 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 60 peer-reviewed papers.
About Natera
NateraTM is a global leader in cell-free DNA and genetic 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 200 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, or our expectations 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.
References
- Zannan et. al. Longitudinal circulating tumor DNA (ctDNA) analysis during treatment (Tx) of locally advanced resectable (LAR) gastric or gastroesophageal junction(G/GEJ) adenocarcinoma (ADENOCA): the PLAGAST prospective biomarker study. 2024 ASCO Annual Meeting. Poster #4028
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9148370/
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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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