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Br J Cancer. 2018 Oct;119(9):1086-1093. doi: 10.1038/s41416-018-0235-2. Epub 2018 Oct 26.

Safety and pharmacokinetics of MM-302, a HER2-targeted antibody-liposomal doxorubicin conjugate, in patients with advanced HER2-positive breast cancer: a phase 1 dose-escalation study.

Author information

1
Helen Diller Family Comprehensive Cancer Center, Department of Medicine, University of California, San Francisco, CA, USA. Pmunster@medicine.ucsf.edu.
2
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
3
Yale Cancer Center, New Haven, CT, USA.
4
Department of Medicine and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.
5
Mallinckrodt Institute of Radiology and the Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO, USA.
6
Department of Oncology, Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA.
7
Research and Development, Merrimack Pharmaceuticals, Inc, Cambridge, MA, USA.
8
Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA.

Abstract

BACKGROUND:

This phase 1 dose-escalation trial studied MM-302, a novel HER2-targeted PEGylated antibody-liposomal doxorubicin conjugate, in HER2-positive locally advanced/metastatic breast cancer.

METHODS:

Patients were enrolled in four cohorts: MM-302 monotherapy (8, 16, 30, 40, and 50 mg/m2 every 4 weeks [q4w]); MM-302 (30 or 40 mg/m2 q4w) plus trastuzumab (4 mg/kg q2w); MM-302 (30 mg/m2) plus trastuzumab (6 mg/kg) q3w; MM-302 (30 mg/m2) plus trastuzumab (6 mg/kg) and cyclophosphamide (450 mg/m2) q3w.

RESULTS:

Sixty-nine patients were treated. The most common adverse events (AEs) were fatigue and nausea. Grade 3/4 AEs of special interest included neutropenia, fatigue, mucosal inflammation, anemia, thrombocytopenia, febrile neutropenia, and palmar-plantar erythrodysesthesia. The MTD was not reached. With MM-302 ≥ 30 mg/m2, overall response rate (ORR) was 13% and median progression-free survival (mPFS) 7.4 months (95% CI: 3·5-10·9) in all arms. In 25 anthracycline-naïve patients, ORR was 28·0% and mPFS 10·9 months (95% CI: 1·8-15·3). Imaging with 64Cu-labeled MM-302 visualized tumor-drug penetrance in tumors throughout the body, including the brain.

CONCLUSION:

MM-302 monotherapy, in combination with trastuzumab, or trastuzumab plus cyclophosphamide, was well tolerated and showed promising efficacy. The selected phase 2 MM-302 dose was 30 mg/m2 plus 6 mg/kg trastuzumab q3w.

PMID:
30361524
PMCID:
PMC6219487
[Available on 2019-10-30]
DOI:
10.1038/s41416-018-0235-2

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