HERMIONE: a randomized Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician’s choice plus trastuzumab in patients with previously treated, anthracycline-naïve, HER2-positive, locally advanced/metastatic breast cancer

BMC Cancer

Study Protocol

Ian E. Krop¹  Kathy Miller²  Debu Tripathy³  Thomas J. Wickham⁴  Kaveh Riahi⁴  Istvan Molnar⁴  Joseph G. Reynolds⁴  Denise A. Yardley⁵  Sunil Verma⁶  Sara A. Hurvitz⁷  Javier Cortes⁸ 

[1] Dana-Farber Cancer Institute, Boston, MA, USA;Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA;MD Anderson Cancer Center, Houston, TX, USA;Merrimack Pharmaceuticals, Inc., 1 Kendall Square, Suite B7201, 02139-1670, Cambridge, MA, USA;Sarah Cannon Research Institute, and Tennessee Oncology, PLLC, Nashville, TN, USA;Sunnybrook Odette Cancer Centre, Toronto, Canada;University of California Los Angeles, Los Angeles, CA, USA;Vall d’Hebron Institute of Oncology (VHIO), Barcelona, Spain and Ramony Cajal University Hospital, Madrid, Spain;

关键词: Advanced/metastatic breast cancer;    Antibody–conjugate;    Doxorubicin;    Cardiotoxicity;    HERMIONE;    Human epidermal growth factor receptor 2/HER2/Erb2;    HER2-targeted liposomal doxorubicin;    Immunoliposome;    MM­302;    Trastuzumab;   

DOI  :  10.1186/s12885-016-2385-z

 received in 2015-11-03, accepted in 2016-05-25,  发布年份 2016

来源: Springer

【 摘 要 】

BackgroundHuman epidermal growth factor receptor 2 (HER2)-positive breast cancer is a particularly aggressive form of the disease, and ultimately progresses in patients with metastases on standard therapies. Anthracyclines, such as doxorubicin, are an effective treatment for HER2-positive breast cancer, particularly when administered in combination with trastuzumab – however, doxorubicin-related cardiotoxicity has limited its use. Many patients are therefore never treated with anthracyclines, even upon disease progression, despite the potential for benefit. MM-302 is a novel, HER2-targeted antibody–liposomal doxorubicin conjugate that specifically targets HER2­overexpressing cells. Preclinical and Phase 1 data suggest that MM-302, as a monotherapy or in combination with trastuzumab, could be effective for managing previously treated, anthracycline-naïve, HER2-positive breast cancer, without the cardiotoxicity observed with free doxorubicin formulations.Methods/DesignHERMIONE is an open-label, multicenter, randomized (1:1) Phase 2 trial of MM-302 plus trastuzumab versus chemotherapy of physician’s choice (gemcitabine, capecitabine, or vinorelbine) plus trastuzumab planned to enroll 250 anthracycline-naïve patients with locally advanced/metastatic HER2-positive breast cancer. Key inclusion criteria are: previous treatment with trastuzumab (with or without pertuzumab) in any setting; refractory or intolerant to pertuzumab (refractory to pertuzumab defined as progression in the locally advanced or metastatic setting, or disease recurrence during or within 12 months of completing pertuzumab-containing neoadjuvant and/or adjuvant therapy); and disease progression on, or intolerant to, ado-trastuzumab emtansine for locally advanced or metastatic disease. The trial is currently being conducted at sites in the USA, Canada, and Western Europe. Treatment will be administered in 21-day cycles, and will be continued until disease progression or unacceptable toxicity. The primary endpoint is independently assessed progression-free survival (PFS). Tumor response will be assessed every 6 weeks, and defined according to RECIST v1.1. Secondary endpoints include investigator-assessed PFS, overall survival (OS), OS rates at 6 months and 1 year, objective response rates, safety and tolerability, quality of life, and the pharmacokinetic profile of MM-302 plus trastuzumab.DiscussionThe HERMIONE study will evaluate the efficacy and safety of MM-302 plus trastuzumab in patients with refractory HER2-positive advanced/metastatic breast cancer for whom there are no standard of care therapies with a proven survival advantage.Trial RegistrationClinicaltrials.gov identifier: NCT02213744. Registration date: 06AUG2014.

【 授权许可】

CC BY   
© The Author(s). 2016