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Successful Readout of Prospective Phase 2 SINERGY Trial Supports SignateraTM MRD-Guided Treatment in Head and Neck Cancer
Interventional trial validates adaptive Signatera-guided treatment approach, achieving strong 63% response rate while reducing chemotherapy exposure in 74%
About this update from Natera, Inc.
[{"type":"text","content":"\nInterventional trial validates adaptive Signatera-guided treatment approach, achieving strong 63% response rate while reducing chemotherapy exposure in 74% of patients\n\n\nResults selected for oral plenary at 2026 Multidisciplinary Head and Neck Cancers Symposium (MHNCS)\n\n\n AUSTIN, Texas--(BUSINESS WIRE)--\nNatera, 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.\n\n\nApproximately 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.\n\n\nIn 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.\n\n\nThe study met its primary endpoint (objective response rate), with the following key highlights:\n\n\n\n74% 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).\n\n\n\nObjective 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.\n\n\n\nSevere 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.\n\n\n\n“The SINERGY trial is unique in that it adapted chemo-immunotherapy treatment guided by ctDNA dynamics...