Abstract CT234: A phase I study of MM-302, a HER2-targeted PEGylated liposomal doxorubicin, in patients with HER2+ metastatic breast cancer
Authors: LoRusso Patricia , Krop Ian , Miller Kathy , Ma Cynthia , Siegel Barry A. , Shields Anthony F. , Molnar Istvan , Wickham Thomas , Reynolds Joseph , Campbell Karen , Hendriks Bart , McClure Ty , Moyo Victor , Munster Pamela 
Published: August 2015

Abstract
Background: MM-302 is an antibody drug conjugated HER2-targeted liposomal doxorubicin in development by Merrimack Pharmaceuticals. MM-302 is designed to deliver doxorubicin to HER2-overexpressing cancer cells with minimal exposure to healthy cardiomyocytes. Results of the MM-302 phase I study as a monotherapy, in combination with trastuzumab and trastuzumab plus cyclophosphamide, are presented.
Methods: 69 patients with HER2-positive metastatic breast cancer (mBC) were treated with either MM-302 alone (8, 16, 30, 40 and 50 mg/m2, Q4W) (Arm 1), MM-302 (30 and 40 mg/m2, Q4W) plus trastuzumab (4 mg/kg, Q2W) (Arm 2), MM-302 (30 mg/m2, Q3W) plus trastuzumab (6 mg/kg, Q3W) (Arm 3), MM-302 (30 mg/m2, Q3W) plus trastuzumab (6 mg/kg, Q3W) and cyclophosphamide (450 mg/m2, Q3W) (Arm 4). Patients on Arms 3 and 4 received a single 3-7 mg/m2 (approximately 10.8 mCi) dose of 64Cu-MM-302 followed by PET/CT to assess for MM-302 tumor deposition.
Results: Patients received a median of 4 prior regimens for mBC. The most common Grade 3/4 side effect was neutropenia observed in 8 patients with 1 patient experiencing febrile neutropenia. Adverse events of any grade occurring in &gt;20% of the population were constipation, cough, decreased appetite, diarrhea, dyspnea, fatigue, nausea, neutropenia, stomatitis and vomiting. Alopecia and hand foot syndrome were observed in 10% and 4% of patients respectively. 1 patient experienced a dose limiting toxicity DLT (febrile neutropenia) and a MTD was not reached at 50 mg/m2. 11 patients received cumulative anthracycline (previous exposure plus MM-302) exposure &gt;550 mg/m2. LVEF reductions below 50% or a &gt;10 percentage point drop in LVEF from baseline occurred in 6 patients. 1 patient experienced Grade 1 cardiac failure resulting in treatment discontinuation. In patients treated with ≥30 mg/m2 MM-302 (n = 49), alone or in combination with trastuzumab, the response rate (RR) was 12% and median progression free survival (mPFS) was 7.6 months (95% CI: 3.6-11.0). mPFS was 10.6 months (95% CI: 1.8-10.6) in the 13 patients receiving MM-302 plus trastuzumab and cyclophosphamide in Arm 4.
Conclusions: MM-302 had a manageable safety profile in this study as a monotherapy, in combination with trastuzumab and with trastuzumab and cyclophosphamide. RR and mPFS in this heavily pretreated mBC population suggest further study is warranted. MM-302 at a dose of 30 mg/m2 Q3W in combination with trastuzumab is currently being evaluated in a randomized phase II trial (HERMIONE) in anthracycline naïve HER2-positive locally advanced/mBC patients previously treated with trastuzumab, pertuzumab and T-DM1.
Citation Format: Patricia LoRusso, Ian Krop, Kathy Miller, Cynthia Ma, Barry A. Siegel, Anthony F. Shields, Istvan Molnar, Thomas Wickham, Joseph Reynolds, Karen Campbell, Bart Hendriks, Ty McClure, Victor Moyo, Pamela Munster. A phase I study of MM-302, a HER2-targeted PEGylated liposomal doxorubicin, in patients with HER2+ metastatic breast cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr CT234. doi:10.1158/1538-7445.AM2015-CT234