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

Natera, Inc., a pioneering force in cell-free DNA testing, has partnered with the Alliance for Clinical Trials in Oncology, a component of the National Clinical Trials Network funded by the National Cancer Institute. Their joint venture, the Alliance A032103 (MODERN) trial, marks a significant step forward in the field of cancer treatment. This phase II/III study will integrate biomarker-based strategies with Natera's Signatera™, a molecular residual disease (MRD) test designed to individualize patient care following radical cystectomy for muscle-invasive urothelial cancer (MIUC).

Urothelial cancer, the most prevalent form of urinary cancer in the United States, sees around 35,000 new diagnoses annually. Despite treatment with cystectomy, about half of the patients experience metastatic recurrence within the first few years.

The MODERN trial plans to enroll nearly 1,000 patients across over 300 North American sites. The trial's innovative design involves the use of Signatera to assess MRD status, subsequently guiding treatment strategies. Patients who test positive for MRD will have their treatment options randomized between nivolumab, a PD-1 antibody, and a combination therapy of nivolumab plus relatlimab, a LAG-3 antibody. The trial also explores treatment de-escalation for MRD-negative patients, offering surveillance with treatment reserved for those who convert to MRD-positive in subsequent tests.

The MODERN trial builds upon the results of the CheckMate 274 trial, which confirmed the safety and efficacy of adjuvant nivolumab in MIUC, leading to its FDA approval. Furthermore, the IMvigor010 trial's findings, published in Nature in 2021, indicated that 63% of MIUC patients tested MRD-negative post-surgery and derived no significant benefit from adjuvant immunotherapy compared to observation.

Matthew Galsky, MD, a prominent figure in bladder cancer research, lauds the MODERN trial as a step towards precision medicine in bladder cancer treatment. He believes that using Signatera to gauge residual cancer after surgery could refine the use of post-surgical immunotherapy and enhance patient care.

Minetta Liu, MD, Natera's Chief Medical Officer of Oncology, draws parallels between MODERN and the CIRCULATE trials in colorectal cancer, emphasizing the potential of Signatera-guided treatment pathways to improve patient outcomes.

Signatera is a personalized molecular residual disease test that leverages circulating tumor DNA to detect residual cancer, anticipate recurrence, and aid in treatment decision-making. It is clinically validated, covered by Medicare for several cancer types, and supported by over 50 peer-reviewed publications.

Natera is a global leader in cell-free DNA testing, focusing on oncology, women's health, and organ health. The company operates certified laboratories in Texas and California and is committed to integrating genetic testing into standard care to enhance health protection and enable earlier, more targeted interventions.

The Alliance for Clinical Trials in Oncology is dedicated to developing and conducting clinical trials for innovative cancer therapies, optimizing cancer treatment and prevention strategies, and researching methods to alleviate cancer treatment side effects. It is a vital part of the U.S. and Canadian cancer research landscape, with nearly 10,000 cancer specialists across various medical facilities.

This trial represents a significant stride towards a more personalized and effective approach to treating muscle-invasive urothelial cancer, potentially leading to better patient outcomes and a new era of precision medicine in oncology.