The circulating tumor DNA (ctDNA)-based detection of molecular residual disease (MRD) may identify patients who are at higher risk for relapse and are therefore candidates for treatment intensification to mitigate this risk. In this context, the addition of the irreversible HER2 tyrosine kinase inhibitor (TKI) neratinib to standard trastuzumab emtansine in the adjuvant setting is being evaluated as an MRD-directed interception strategy in patients with HER2-positive breast cancer and MRD positivity.
The KAN-HER2 MRD trial is a multicenter, investigator-initiated, open-label, single-arm, phase 2 study that is evaluating the addition of neratinib to standard trastuzumab emtansine in patients with HER-2 positive breast cancer and MRD. The study inclusion criteria are age ≥18 years; having histologically confirmed, resected, HER2-positive stage I to III breast cancer; and having evidence of residual invasive disease after previous neoadjuvant trastuzumab-based chemotherapy (with or without pertuzumab) or while receiving 2 to 6 cycles of adjuvant trastuzumab emtansine. The study exclusion criteria include previous therapy with any HER2 TKI and evidence of suspected or confirmed metastatic breast cancer. MRD is detected using a tumor-informed assay (NeoGenomics RaDaR) in patients who have received neoadjuvant therapy or 2 to 6 cycles of adjuvant trastuzumab emtansine. Eligible patients with evidence of MRD will receive neratinib in addition to standard trastuzumab emtansine at the previously determined recommended phase 2 combination dose of 160 mg/day, in continuous cycles.
The primary end point is the rate of ctDNA clearance at 12 weeks after treatment initiation; the secondary end points include MRD rates and their clinical correlates, invasive-disease-free survival, and safety. Correlative studies will be performed on samples collected from diagnostic biopsies, residual disease, and the peripheral blood of enrolled patients.
The estimated enrollment is 15 patients. Enrollment in the study was initiated at the first trial site (Princess Margaret Cancer Centre, Toronto, Ontario, Canada) in December 2022. The estimated study completion date is July 2025.
Source: Elliott M, Antrás JF, Echelard P, et al. A phase II single-arm, open-label trial of T-DM1 (ado-trastuzumab emtansine) and neratinib for HER2-positive breast cancer with molecular residual disease (KAN-HER2 MRD). Abstract presented at: ASCO Annual Meeting, June 2-6, 2023; Chicago, IL. Abstract TPS620.