Abstract CT234: A phase I study of MM-302, a HER2-targeted PEGylated liposomal doxorubicin, in patients with HER2+ metastatic breast cancer
Authors: 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
Journal: Cancer Research (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 &amp;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 &amp;gt;550 mg/m2. LVEF reductions below 50% or a &amp;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