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

47 Citations (Scopus)

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

Anthracyclines
Breast Neoplasms
Physicians
Drug Therapy
Doxorubicin
Disease Progression
gemcitabine
Disease-Free Survival
Therapeutics
Safety
Survival
Standard of Care
Trastuzumab
human ERBB2 protein
Canada
Survival Rate
Pharmacokinetics
Quality of Life
Research Personnel
Neoplasm Metastasis

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

  • Oncology
  • Cancer Research
  • Genetics

Cite this

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

In: BMC Cancer, Vol. 16, No. 1, 352, 03.06.2016.

Research output: Contribution to journalArticle

Miller, Kathy ; Cortes, Javier ; Hurvitz, Sara A. ; Krop, Ian E. ; Tripathy, Debu ; Verma, Sunil ; Riahi, Kaveh ; Reynolds, Joseph G. ; Wickham, Thomas J. ; Molnar, Istvan ; Yardley, Denise A. / 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. In: BMC Cancer. 2016 ; Vol. 16, No. 1.
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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-na{\"i}ve, 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-na{\"i}ve 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.",
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T2 - 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

AU - Miller, Kathy

AU - Cortes, Javier

AU - Hurvitz, Sara A.

AU - Krop, Ian E.

AU - Tripathy, Debu

AU - Verma, Sunil

AU - Riahi, Kaveh

AU - Reynolds, Joseph G.

AU - Wickham, Thomas J.

AU - Molnar, Istvan

AU - Yardley, Denise A.

PY - 2016/6/3

Y1 - 2016/6/3

N2 - 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.

AB - 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.

KW - Advanced/metastatic breast cancer

KW - Antibody-conjugate

KW - Cardiotoxicity

KW - Doxorubicin

KW - HER2-targeted liposomal doxorubicin

KW - HERMIONE

KW - Human epidermal growth factor receptor 2/HER2/Erb2

KW - Immunoliposome

KW - MM302

KW - Trastuzumab

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