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 breReport as inadecuate




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 bre - Download this document for free, or read online. Document in PDF available to download.

BMC Cancer

, 16:352

Medical and radiation oncology

Abstract

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.

KeywordsAdvanced-metastatic breast cancer Antibody–conjugate Doxorubicin Cardiotoxicity HERMIONE Human epidermal growth factor receptor 2-HER2-Erb2 HER2-targeted liposomal doxorubicin Immunoliposome MM­302 Trastuzumab Previous presentation: Miller K et al. San Antonio Breast Cancer Symposium SABCS 2015, Poster OT3-01-01

Electronic supplementary materialThe online version of this article doi:10.1186-s12885-016-2385-z contains supplementary material, which is available to authorized users.

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Author: Kathy Miller - Javier Cortes - Sara A. Hurvitz - Ian E. Krop - Debu Tripathy - Sunil Verma - Kaveh Riahi - Joseph G. Re

Source: https://link.springer.com/







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