Natera and Alliance for Clinical Trials in Oncology Announce Activation of Alliance A032103 (MODERN)

A Randomized, Phase II/III Adjuvant Trial in Urothelial Cancer

Natera, Inc. (NASDAQ: NTRA), a global leader in cell-free DNA testing, and the Alliance for Clinical Trials in Oncology, which is part of the National Clinical Trials Network (NCTN) funded by the National Cancer Institute (NCI), part of National Institutes of Health, today announced the launch of Alliance A032103 (MODERN), a randomized, phase II/III, biomarker-integrated trial. Alliance A032103 (MODERN) will utilize Signatera, Natera’s personalized and tumor-informed molecular residual disease (MRD) test, to help guide personalized treatment based on molecular status in patients diagnosed with muscle-invasive urothelial cancer (MIUC) after radical cystectomy.

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Urothelial cancer is the most common urinary cancer diagnosed in the United States, and approximately 35,000 patients per year are diagnosed with localized and locally advanced urothelial cancer.¹ Approximately 50% of patients treated with cystectomy will develop metastatic recurrence within 2-3 years.^2,3

In the Alliance A032103 (MODERN) trial, approximately 1,000 patients will be enrolled at more than 300 sites in North America. Patients will be divided into two cohorts based on an initial assessment of MRD status. Patients who are Signatera MRD-positive will have treatment randomized to either nivolumab, a PD-1 antibody, or escalation with nivolumab, a PD-1 antibody plus relatlimab, a LAG-3 antibody; LAG-3 and PD-1 are distinct inhibitory immune checkpoints. Patients who are Signatera MRD-negative will be randomized to either nivolumab, a standard of care therapy, or de-escalation to surveillance, with the surveilled patients receiving treatment only upon future conversion to MRD-positive status based on serial testing.

This trial was made possible by results of the pivotal CheckMate 274 trial,⁴ which established the safety and efficacy of adjuvant nivolumab in MIUC, and is now the only FDA-approved therapy in this disease setting.⁵ Additionally, data published in the journal Nature in 2021 from the IMvigor010 trial showed that 63% of patients with MIUC tested Signatera MRD-negative after surgery, and those patients received no significant benefit from adjuvant immunotherapy (atezolizumab) versus observation.⁶