Natera and Alliance Foundation Trials (AFT) have launched a randomized phase III trial testing whether molecular residual disease (MRD) monitoring can determine which patients with intermediate- and high-risk ER-positive/HER2-negative early breast cancer need adjuvant treatment.
The AFT-70 NAVIGATE trial, announced Oct. 5, pairs Genentech’s giredestrant, a selective estrogen receptor degrader, with longitudinal monitoring using Natera’s Signatera Genome MRD test.
AFT is sponsoring and leading the study, with collaboration and funding from both Natera and Genentech. Financial terms of the collaboration were not disclosed.
The study is designed to test whether patients can maintain outcomes when CDK4/6 inhibitors are used more selectively, rather than giving all patients prolonged combination therapy.
“We know that patients with ER-positive, HER2-negative breast cancer do not all face the same risk of recurrence, yet adjuvant treatment decisions are still largely based on clinical and pathological features measured at diagnosis,” Komal Jhaveri, the study chair and an oncologist at Memorial Sloan Kettering Cancer Center, said in a statement. “The trial will determine whether MRD-guided monitoring can distinguish patients most likely to benefit from adding a CDK4/6 inhibitor from those in whom it can be safely omitted. It’s an important step forward using biology—not just baseline risk—to guide adjuvant therapy.”
AFT expects to enroll more than 2,000 patients with stage II-III ER-positive/HER2-negative breast cancer who are eligible for endocrine therapy, at about 200 sites in the US and internationally.
The control arm will receive standard-of-care endocrine therapy plus upfront CDK4/6 inhibition. The investigational arm will receive giredestrant alone, with a CDK4/6 inhibitor added only if Signatera becomes positive. The primary endpoint is non-inferiority in four-year distant recurrence-free survival. The partners did not say when enrollment will begin or when results are expected.
The study is the latest de-escalation trial evaluating the use of MRD to help spare patients with solid tumors extra treatment without harming their survival odds. Trials using a similar approach in colorectal cancer include the DYNAMIC and VEGA.