Launch of Phase II/III MODERN Trial for Adjuvant Urothelial Cancer Treatment

A groundbreaking clinical trial focusing on muscle-invasive urothelial cancer (MIUC) has been initiated. The study, known as Alliance A032103 or MODERN, is a collaborative effort between Natera, Inc., a leading company in cell-free DNA testing, and the Alliance for Clinical Trials in Oncology, which is part of the National Clinical Trials Network funded by the National Cancer Institute. This randomized phase II/III trial will incorporate Natera's Signatera™, a molecular residual disease (MRD) test, to guide personalized treatment strategies for patients post-radical cystectomy.

Urothelial cancer is the most prevalent form of urinary cancer in the United States, with an estimated 35,000 new diagnoses annually. The disease has a high recurrence rate, with about half of the patients developing metastases within the first few years following surgery.

The trial plans to enroll around 1,000 patients across over 300 North American sites. Participants will be categorized into two groups based on their initial MRD status as determined by Signatera. Those testing positive for MRD will have their treatment randomized to either nivolumab—a PD-1 antibody—or an escalated treatment involving both nivolumab and relatlimab, a LAG-3 antibody. The trial design also includes a de-escalation arm for patients testing negative for MRD, where they will be monitored and treated only if their status changes to positive in the future.

This initiative follows the successful CheckMate 274 trial, which confirmed the safety and efficacy of adjuvant nivolumab in MIUC, leading to its FDA approval. Furthermore, findings published in Nature from the IMvigor010 trial indicated that patients with MIUC who tested negative for MRD post-surgery did not benefit significantly from adjuvant immunotherapy.

The MODERN trial is expected to advance precision medicine in bladder cancer treatment by customizing immunotherapy post-surgery based on individual molecular profiles. This approach aims to optimize patient care by delivering more targeted treatments. The study also highlights the potential of Signatera-guided treatment pathways to enhance patient outcomes, similar to the CIRCULATE trials conducted for colorectal cancer.

Natera's Signatera is a personalized molecular residual disease test that uses circulating tumor DNA to detect remaining cancer in the body post-diagnosis. It is designed to identify cancer recurrence earlier than traditional methods and assist in making more informed treatment decisions. The test is clinically validated and supported by Medicare for various cancer types, including colorectal, breast, ovarian, and muscle-invasive bladder cancer.

Natera is a global leader in cell-free DNA testing, with a focus on oncology, women's health, and organ health. The company operates certified laboratories in Texas and California and has over 180 peer-reviewed publications validating the accuracy of its tests.

The Alliance for Clinical Trials in Oncology is dedicated to developing and conducting clinical trials for innovative cancer therapies. It is part of the National Clinical Trials Network and comprises nearly 10,000 cancer specialists across the United States and Canada.