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.
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.



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 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.



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.



Clinicaltrials.gov identifier: NCT02213744 . Registration date: 06AUG2014.
Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.
Kathy
K
Miller
Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain and Ramony Cajal University Hospital, Madrid, Spain.
Javier
J
Cortes
University of California Los Angeles, Los Angeles, CA, USA.
Sara A
SA
Hurvitz
Dana-Farber Cancer Institute, Boston, MA, USA.
Ian E
IE
Krop
MD Anderson Cancer Center, Houston, TX, USA.
Debu
D
Tripathy
Sunnybrook Odette Cancer Centre, Toronto, Canada.
Sunil
S
Verma
Merrimack Pharmaceuticals, Inc., 1 Kendall Square, Suite B7201, Cambridge, MA, 02139-1670, USA.
Kaveh
K
Riahi
Merrimack Pharmaceuticals, Inc., 1 Kendall Square, Suite B7201, Cambridge, MA, 02139-1670, USA. jreynolds@merrimackpharma.com.
Joseph G
JG
Reynolds
Merrimack Pharmaceuticals, Inc., 1 Kendall Square, Suite B7201, Cambridge, MA, 02139-1670, USA.
Thomas J
TJ
Wickham
Merrimack Pharmaceuticals, Inc., 1 Kendall Square, Suite B7201, Cambridge, MA, 02139-1670, USA.
Istvan
I
Molnar
Sarah Cannon Research Institute, and Tennessee Oncology, PLLC, Nashville, TN, USA.
Denise A
DA
Yardley
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D000922:Immunotoxins / Q000627:therapeutic use; D058990:Molecular Targeted Therapy / Q000379:methods*; D009362:Neoplasm Metastasis; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors; D012107:Research Design; D057127:Single-Chain Antibodies / Q000627:therapeutic use*; D000068878:Trastuzumab / Q000008:administration & dosage / Q000009:adverse effects
D004317:Doxorubicin; D018796:Immunoconjugates; D000922:Immunotoxins; D011092:Polyethylene Glycols; D018719:Erb-b2 Receptor Tyrosine Kinases; D057127:Single-Chain Antibodies; D000068878:Trastuzumab; C506643:liposomal doxorubicin; C508053:ERBB2 protein, human; C000624282:gancotamab
Advanced/metastatic breast cancer; Antibody–conjugate; Cardiotoxicity; Doxorubicin; HER2-targeted liposomal doxorubicin; HERMIONE; Human epidermal growth factor receptor 2/HER2/Erb2; Immunoliposome; MM­302; Trastuzumab