Boston-based Alliance Foundation Trials (AFT) and Austin, Texas-based Natera (Nasdaq: NTRA) have launched AFT-70 NAVIGATE, a Phase III trial testing whether patients with no detectable molecular residual disease (MRD) after treatment for early breast cancer can safely defer CDK4/6 inhibitor therapy.
The study will enrol more than 2,000 patients with intermediate- or high-risk, stage II–III ER-positive/HER2-negative breast cancer at approximately 200 sites across the US and internationally. AFT sponsors and leads the trial, with collaboration and co-funding from Natera and Genentech, a member of the Roche Group.
Patients who are MRD-negative after standard treatment will be randomized to standard endocrine therapy plus upfront CDK4/6 inhibition, or Genentech’s investigational oral selective estrogen receptor degrader (SERD) giredestrant alone. In the investigational arm, a CDK4/6 inhibitor will be added only if longitudinal monitoring with Natera’s Signatera Genome test detects MRD.
The primary endpoint is non-inferiority in four-year distant recurrence-free survival: whether the investigational strategy preserves protection against distant recurrence while potentially reducing CDK4/6 inhibitor exposure. Because the arms differ in both endocrine therapy and the timing of CDK4/6 treatment, the trial evaluates the complete treatment strategy.