Natera Unveils Phase II DECIPHER Trial for Gastroesophageal Cancer

Natera, Inc., a leading company in the field of cell-free DNA (cfDNA) and genetic testing, has announced a new clinical trial called DECIPHER that aims to explore the efficacy of a novel HER2-directed adjuvant treatment in patients with gastroesophageal adenocarcinoma. This trial is notable for its use of Natera's personalized and tumor-informed molecular residual disease (MRD) test, Signatera™, to guide treatment decisions and monitor the rate of MRD clearance.

The DECIPHER trial, officially titled Developing ctDNA Guided Adjuvant Therapy for Gastroesophageal Cancer, is a single-arm, open-label phase II study. It is the first of its kind to investigate the effectiveness of a HER2-directed antibody-drug conjugate specifically for gastroesophageal adenocarcinoma (EGC) patients in an adjuvant setting. The study intends to enroll 25 participants from over ten sites across the United Kingdom. Patients who test positive for MRD using Signatera after undergoing neoadjuvant chemotherapy and surgical procedures will skip standard adjuvant chemotherapy and receive the investigational treatment for up to eight cycles. The primary endpoint of the study is the clearance of MRD, which will be measured periodically using Signatera.

Dr. Elizabeth Smyth, a consultant in medical oncology at Oxford University Hospitals NHS Foundation Trust, highlighted the potential impact of this approach. She noted that DECIPHER aims to offer patients an additional opportunity for a cure when standard therapies have failed. She emphasized the importance of Signatera's personalized, tumor-informed methodology, which has shown high sensitivity across various cancer types, including EGC.

The trial's launch follows compelling data from the PLAGAST study, which was presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. This study revealed that EGC patients who remained MRD-positive after receiving neoadjuvant FLOT chemotherapy and surgical resection faced a very high risk of disease progression within 12 months, despite undergoing standard adjuvant treatment. These patients also had a zero percent overall survival rate at 24 months.

Gastroesophageal cancer is a globally prevalent cancer with a growing incidence rate, nearly 2.5 times higher over the past two decades. Typically, patients with early-stage disease undergo an aggressive treatment regimen that includes neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy. Despite this comprehensive approach, curative outcomes are achieved in less than half of the cases.

Dr. Adham Jurdi, Senior Medical Director of Oncology at Natera, expressed satisfaction in collaborating with leading UK investigators on this pivotal trial. He highlighted that DECIPHER aims to showcase how integrating Signatera with innovative therapies can potentially offer new personalized treatment options and enhance outcomes for EGC patients.

The DECIPHER trial will be showcased in a poster presentation at the European Society for Medical Oncology Gastrointestinal Cancers (ESMO GI) Congress 2024 in Munich, Germany. The poster is titled "A single arm phase II trial of trastuzumab deruxtecan in patients with gastro-oesophageal adenocarcinoma cancer who are ctDNA and HER2 positive: DECIPHER."

Signatera is a personalized, tumor-informed molecular residual disease test designed for patients previously diagnosed with cancer. It leverages circulating tumor DNA to detect and quantify residual cancer in the body, identify recurrence earlier than conventional methods, and aid in optimizing treatment decisions. Signatera has been clinically validated across multiple cancer types and is available for both clinical and research applications. It is covered by Medicare for several cancer types, including colorectal, breast, ovarian, and muscle-invasive bladder cancers, as well as for immunotherapy monitoring of any solid tumor.

Natera, Inc. is a global leader in cell-free DNA and genetic testing, committed to advancing oncology, women's health, and organ health through personalized genetic testing and diagnostics. The company's tests are supported by extensive peer-reviewed research and are conducted in certified laboratories in Austin, Texas, and San Carlos, California.