Abstract OT3-01-01: HERMIONE: A phase 2, randomized, open label trial comparing MM-302 plus trastuzumab with chemotherapy of physician's choice plus trastuzumab, in anthracycline naive HER2-positive, locally advanced/metastatic breast cancer patients previously treated with pertuzumab and ado-trastuzumab emtansine (T-DM1)

Abstract

Abstract Background: Although HER2-targeted therapies such as pertuzumab and T-DM1 have improved patient outcomes, treatment resistance typically occurs. MM-302 is a HER2-targeted liposomal doxorubicin in development by Merrimack Pharmaceuticals. In a Phase 1 study, patients with HER2-positive metastatic breast cancer (MBC) were treated with MM-302 alone and in combination with trastuzumab with or without cyclophosphamide. MM-302 had an acceptable safety profile and promising efficacy was observed in patients not previously exposed to an anthracycline. Trial design: HERMIONE (NCT02213744) is a randomized Phase 2, two-arm, open-label trial designed to evaluate if MM-302 can address an unmet medical need in patients with anthracycline naïve, trastuzumab-, pertuzumab- and T-DM1-pretreated HER2-positive locally advanced breast cancer (LABC)/MBC. Patients are randomized 1:1 to receive MM-302 (30mg/m2, Q3W) plus trastuzumab (6mg/kg, Q3W) or chemotherapy of physician's choice (vinorelbine, capecitabine, or gemcitabine) plus trastuzumab (6mg/kg, Q3W). Eligibility criteria: Centrally confirmed HER2-positive LABC/MBC, no prior anthracycline exposure, prior trastuzumab in any setting, prior pertuzumab and T-DM1 in the LABC/MBC setting, unlimited prior lines of therapy, ECOG 0-1 and LVEF ≥50%. CNS metastases are permitted if stable and without symptoms or steroids for 4 weeks. Specific aims: The primary endpoint is independently assessed progression free survival (PFS). Secondary endpoints include investigator assessed PFS, overall survival, response rate, safety and patient related outcomes. Statistics: 250 patients will be enrolled to observe 191 PFS events for 90% power to detect a Hazard Ratio of 0.625. The MM-302 arm will be compared to the control arm on the primary endpoint of PFS using a stratified log-rank test at one-sided 0.025 level. Accrual status: First patient in was December 2014 and enrollment is expected to be complete in late 2016. Sites are open in the US, Canada and Western Europe and are currently enrolling patients. Citation Format: Miller K, Cortes J, Hurvitz SA, Krop IE, Tripathy D, Verma S, Riahi K, Reynolds JG, Wickham T, Molnar I, Yardley DA. HERMIONE: A phase 2, randomized, open label trial comparing MM-302 plus trastuzumab with chemotherapy of physician's choice plus trastuzumab, in anthracycline naive HER2-positive, locally advanced/metastatic breast cancer patients previously treated with pertuzumab and ado-trastuzumab emtansine (T-DM1). [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT3-01-01.