Successful Readout of Prospective Phase 2 SINERGY Trial Supports SignateraTM MRD-Guided Treatment in Head and Neck Cancer

Key Terms

mrd medical

MRD stands for minimal residual disease, the tiny number of cancer cells that can remain in the body after treatment and that may not show up on routine scans. Detecting MRD is like finding a few seeds left in a garden after clearing: it helps doctors predict the chance of relapse and measure how effective a therapy is, which investors watch because MRD results can influence clinical trial success, regulatory decisions, and a drug’s market potential.

circulating tumor dna medical

Fragments of DNA shed by cancer cells into the bloodstream that act like tiny fingerprints of a tumor; they can be detected with a blood test rather than a biopsy. Investors care because circulating tumor DNA (ctDNA) enables faster, lower-cost ways to detect disease, track treatment response, identify emerging resistance and enroll patients in trials—factors that can materially affect the commercial prospects of diagnostics and therapeutics.

ctdna medical

Circulating tumor DNA (ctDNA) is tiny fragments of genetic material shed by cancer cells into the bloodstream, like breadcrumbs that can reveal a tumor’s presence and genetic makeup without needing a biopsy. For investors, ctDNA matters because tests and technologies that detect and analyze these fragments can speed diagnosis, track treatment response, and signal relapse, creating commercial opportunities in diagnostics, personalized therapies, and monitoring services.

immune checkpoint inhibition medical

Immune checkpoint inhibition is a cancer treatment approach that blocks natural “brakes” on the immune system so white blood cells can better recognize and attack tumors; think of lifting a speed limiter so the body’s defences can work harder. It matters to investors because these therapies can drive large sales if proven safe and effective, but their value depends on clinical trial results, regulatory approval, side-effect profiles and competition within a fast-moving field.

objective response rate medical

The objective response rate (ORR) is the percentage of patients in a clinical trial whose tumors measurably shrink or disappear according to preset rules. Investors use it as a quick, objective signal of a drug’s ability to produce a clear treatment effect—like counting how many plants visibly respond after applying a new fertilizer—and higher ORR can improve odds of regulatory approval, commercial success, and company valuation.

grade ≥3 medical

Grade ≥3 indicates an adverse medical event judged at level three or higher on the standard clinical severity scale used in drug and device trials, meaning the problem is severe, medically significant, or potentially life‑threatening. For investors, these higher‑grade events are critical because they can pause or complicate development, prompt additional studies or regulatory scrutiny, and materially change a program’s timeline, cost, and commercial prospects — like a red light stopping a project.

Interventional trial validates adaptive Signatera-guided treatment approach, achieving strong 63% response rate while reducing chemotherapy exposure in 74% of patients

Results selected for oral plenary at 2026 Multidisciplinary Head and Neck Cancers Symposium (MHNCS)

AUSTIN, Texas--(BUSINESS WIRE)-- Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA and precision medicine, today announced results from the SINERGY trial, a Phase 2 study in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). Data was recently presented in an oral plenary at the 2026 MHNCS.

Approximately 73K patients are diagnosed with head and neck cancer in the U.S. annually.¹ The current standard of care for R/M HNSCC patients, based on the registrational KEYNOTE-048 trial, is immune checkpoint inhibition (ICI) either alone, or combined with chemotherapy; however, these regimens are suboptimal with efficacy and toxicity concerns. To help address these issues, SINERGY (NCT05420948) investigated whether personalized circulating tumor DNA (ctDNA) monitoring with Signatera can provide an early signal of treatment efficacy, enabling adaptive escalation or de-escalation of chemotherapy without reducing therapeutic benefit.

In the trial, 27 patients received initial treatment of either immunotherapy alone or in combination with chemotherapy. Based on Signatera ctDNA dynamics during treatment (ctDNA levels rising or falling), chemotherapy was either escalated or de-escalated.

The study met its primary endpoint (objective response rate), with the following key highlights:

• 74% of patients (20/27) were de-escalated from chemo-immunotherapy to immunotherapy alone, resulting in a median of 2 chemotherapy cycles across the full cohort, a substantial two-thirds reduction from the current standard of care (6 cycles).
• Objective response rate (ORR) was strong at 63% (17/27; 95% CI: 42.4–80.6), comparing favorably to the 36% and 19% ORRs from KEYNOTE-048 patients receiving ICI with and without chemotherapy, respectively.
• Severe toxicity of grade ≥3 was 48.1% (13/27), substantially lower than the 85% and 55% from KEYNOTE-048 patients receiving ICI with and without chemotherapy, respectively.

“The SINERGY trial is unique in that it adapted chemo-immunotherapy treatment guided by ctDNA dynamics. The trial demonstrated a promising response rate and survival, with roughly three-quarters of patients experiencing treatment de-escalation guided by ctDNA dynamics,” said Ari J. Rosenberg, M.D., associate professor of medicine at the University of Chicago and presenting author of the study. “This led to a reduction in the number of chemotherapy cycles along with lower rates of high-grade toxicity compared with historical controls. With these results, there is great potential for ctDNA dynamics to optimize treatment in R/M HNSCC.”

“This trial was designed to address an urgent need for treatment personalization that mitigates unnecessary toxicity while improving survival for patients with recurrent or metastatic head and neck cancer,” said Alexey Aleshin, M.D., general manager of oncology and corporate chief medical officer at Natera. “We saw remarkable results that Signatera can inform therapeutic decision-making in real-time for this aggressive and difficult-to-treat cancer, laying the groundwork for changes in the standard of care.”

References

1. National cancer institute SEER (surveillance, epidemiology, and end results) estimate.

About Natera

Natera™ is a global leader in cell-free DNA and precision medicine, 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 supported by more than 350 peer-reviewed publications that demonstrate excellent performance. Natera operates ISO 13485-certified and CAP-accredited laboratories certified under the Clinical Laboratory Improvement Amendments (CLIA) in Austin, Texas, and San Carlos, California, and through Foresight Diagnostics, its subsidiary, operates an ISO 27001-certified and CAP-accredited laboratory certified under CLIA in Boulder, Colorado. For more information, visit www.natera.com.

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.

View source version on businesswire.com: https://www.businesswire.com/news/home/20260224679603/en/

Investor Relations: Mike Brophy, CFO, Natera, Inc., investor@natera.com

Media: Lesley Bogdanow, VP of Corporate Communications, Natera, Inc., pr@natera.com

Source: Natera, Inc.