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

Kathy Miller, Javier Cortes, Sara A. Hurvitz, Ian E. Krop, Debu Tripathy, Sunil Verma, Kaveh Riahi, Joseph G. Reynolds, Thomas J. Wickham, Istvan Molnar, Denise A. Yardley

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

Background: Human 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 HER2-overexpressing 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/Design: HERMIONE 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 12months 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 6weeks, and defined according to RECIST v1.1. Secondary endpoints include investigator-assessed PFS, overall survival (OS), OS rates at 6months and 1year, objective response rates, safety and tolerability, quality of life, and the pharmacokinetic profile of MM-302 plus trastuzumab. Discussion: The 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 Registration: Clinicaltrials.gov identifier: NCT02213744. Registration date: 06AUG2014.

Original languageEnglish (US)
Article number352
JournalBMC Cancer
Volume16
Issue number1
DOIs
StatePublished - Jun 3 2016

    Fingerprint

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Cancer Research

Cite this