315TiP - 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 T-DM1

Abstract

Although HER2-targeted therapies such as pertuzumab and ado-trastuzumab emtansine (T-DM1) have improved patient outcomes, treatment resistance typically occurs. MM-302 is a HER2-targeted antibody-liposomal doxorubicin conjugate 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 is a randomized Phase 2, two-arm, open-label trial 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, prior T-DM1 in the LABC/MBC setting, prior pertuzumab in LABC/MBC setting or disease recurrence within 12 months of neoadjuvant/adjuvant treatment, unlimited prior lines, 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 progression free survival (PFS) assessed by an independent blinded review. 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 HR 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. Status: First patient treated was in December 2014 and enrollment is expected to be complete in 2017. Sites are open in the US, Canada and Western Europe. Clinical trial identification: NCT02213744 Legal entity responsible for the study: Merrimack Pharmaceuticals