Boston– Alliance Foundation Trials and Natera have launched AFT-70 NAVIGATE, a global randomized Phase III trial evaluating a molecular residual disease-guided treatment strategy for patients with intermediate- and high-risk ER-positive/HER2-negative early breast cancer.
The study is sponsored and led by Alliance Foundation Trials, with collaboration and co-funding from Natera and Genentech.
The trial will evaluate whether patients can maintain strong outcomes while using CDK4/6 inhibitors more selectively, rather than exposing all patients to prolonged combination therapy.
The investigational strategy combines Genentech’s giredestrant, an oral selective estrogen receptor degrader, with Natera’s Signatera Genome molecular residual disease test. Patients in the investigational arm will receive giredestrant alone, with a CDK4/6 inhibitor added only if Signatera detects MRD.
Giredestrant was selected based on findings from the Phase III lidERA trial, which showed an improvement in invasive disease-free survival compared with standard endocrine monotherapy in patients with ER-positive/HER2-negative early breast cancer.
Signatera was selected based on clinical evidence in early breast cancer and its newer genome-based technology, which is designed to detect very low levels of residual disease.
Alliance Foundation Trials expects to enroll more than 2,000 patients with stage II-III ER-positive/HER2-negative breast cancer at about 200 sites in the United States and internationally.
Patients with no detectable MRD after completing standard treatment will be randomly assigned either to standard endocrine therapy plus upfront CDK4/6 inhibition or to giredestrant monotherapy with CDK4/6 inhibition added only if MRD becomes detectable.
The primary endpoint is non-inferiority in four-year distant recurrence-free survival.
“This collaboration brings together leading expertise in breast cancer research, clinical care, and molecular testing to address an important question for patients: How can we make treatment more precise while avoiding unnecessary toxicity?” said Evanthia Galanis, M.D., D.Sc., President of Alliance Foundation Trials.
Komal Jhaveri, M.D., Study Chair and Breast Medical Oncologist at Memorial Sloan Kettering Cancer Center, said the study will test whether MRD monitoring can identify patients most likely to benefit from adding a CDK4/6 inhibitor.
“More treatment is not always better treatment,” said Gaorav Gupta, M.D., Ph.D., Study Co-Chair and Co-Leader of the Breast Cancer Research Program at UNC Lineberger Comprehensive Cancer Center.
Minetta Liu, M.D., Chief Medical Officer for Oncology and Early Cancer Detection at Natera, said the trial could help expand more personalized treatment options for patients with higher-risk hormone receptor-positive breast cancer.
