Classifying for HER2 Dependence to De-Escalate Neoadjuvant Chemotherapy in Patients With HER2+ Early Breast Cancer Undergoing HER2 Double-Blockade

This study aims to identify HER2-positive early-stage breast cancer patients who could benefit from neoadjuvant treatment using PHESGO™ (pertuzumab and trastuzumab) without chemotherapy. The approach involves utilizing specific biomarkers (HR and HER2 IHC status) to select participants whose tumors strongly rely on the HER2 pathway, potentially benefiting from a HER2-targeted approach without chemotherapy concurrently.

This is a nonrandomized phase II single arm study to assess de-escalation of chemotherapy in participants with HER2-positive early breast cancer undergoing neoadjuvant therapy with PHESGO™. Participants will be evaluated by central laboratory review for confirmation of selected biomarkers (pre-screening). Participants who meet the biomarker assessment criteria will follow the eligibility criteria assessment. Participants with HER2 positive disease that meet the eligibility criteria will be treated with neoadjuvant PHESGO™. A baseline PET/CT will be performed prior to start of PHESGO™ treatment. All participants will receive fixed-dose subcutaneous formulation with pertuzumab and trastuzumab (PHESGO™) every 21 days for 3 cycles to evaluate PET/CT response. After the 3rd cycle, participants achieving PET/CT response (defined in this trial as ≥40% reduction in the SUVMax as calculated by the formula SUVbaseline SUVresponse/SUVbaseline) will continue treatment with PHESGO™ for 5 additional cycles, completing 8 neoadjuvant cycles of PHESGO™. Participants without PET/CT response after 3rd cycle will be out of study and will receive treatment and surgery according to institutional standard of care. For this cohort of participant, data regarding treatment received, pCR status and outcomes will be collected. Definitive breast cancer surgery will be performed after the 8th cycle of therapy. After surgery, participants will receive adjuvant treatment according to their response. Participants achieving pCR will receive PHESGO™ alone as adjuvant treatment to complete a total of one year of therapy, thus receiving 10 cycles of adjuvant PHESGO™. Participants not achieving pCR will receive one of two adjuvant therapy options as per investigator's choice: (1) 14 cycles of trastuzumab emtansine (T-DM1), or (2) investigator's choice chemotherapy regimen (up to 6 cycles) plus 10 cycles of PHESGO™. Disease status and survival data collection will be abstracted from medical records for up to 5 years after surgery. Participants will be followed for recurrence and survival data with abstraction of data from medical records every 3 months in first year after surgery; every 4 months in second and third years; and then annually until five years. Medical procedures and therapies in the follow-up period are not a formal investigational part of this clinical trial and therefore will be performed according to the institutional standard of care.