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Ian Krop, MD, PhD
Chief of Breast Medical Oncology
Director, Clinical Research for the Breast Oncology Program
Associate Professor of Medicine, Harvard Medical School
Dana-Farber Cancer Institute
Seeking to identify novel predictive markers and therapeutic targets to improve outcomes for patients with advanced HER2-positive in breast cancer.
A clinical trial is planned to test the benefit of adding dual immunotherapy drugs with HER2-directed therapies, compared to HER2 therapy plus a single immunotherapy drug.
This trial will be the first to test dual immunotherapy agents with anti-HER2 agents and will provide important predictive and biomarker data.
HER2-targeted therapies, such as trastuzumab (Herceptin®), have dramatically improved outcomes for many patients with HER2-positive breast cancer. Today, there are several FDA-approved drugs for HER2-positive breast cancer. Many patients, however, will progress on one or more of these drugs and develop metastatic disease. Immunotherapy has recently been shown to counter tumor resistance to HER2-directed therapy. Drs. Krop and Loi are conducting a clinical trial in patients with metastatic HER2-positive breast cancer to see if immunotherapy combinations can improve response to trastuzumab.
Full Research Summary
HER2-positive breast cancer is an aggressive form of breast cancer when untreated. Drugs that specifically target HER2, such as trastuzumab, have improved outcomes, but metastatic HER2-positive breast cancer is still incurable and resistance to trastuzumab and other HER2-directed agents remains a critical problem.
While trastuzumab effectively targets the HER2 protein, it may also cause an anti-tumor immune response. In laboratory studies, the addition of trastuzumab enhanced the tumor cell killing effect of dual immunotherapy.
In this randomized phase II clinical trial, conducted through the Tranlational Breast Cancer Research Consortium (TBCRC), Dr. Krop and BCRF collaborator, Dr. Sherene Loi, will compare progression-free survival in patients with advanced HER2-positive breast cancer who receive a combination of trastuzumab plus two immunotherapy drugs to patients receiving trastuzumab and a single immunotherapy.They will collect tumor tissue before and after treatment to identify biomarkers to predict benefit of the dual immunotherapy combination.
Metastatic HER2-positive breast cancer remains a significant clinical concern. This trial may identify an alternative strategy for patients who do not respond to trastuzumab.
Ian Elliott Krop, MD, PhD, is the Chief of Breast Medical Oncology and the Director of Clinical Research for the Breast Oncology Program at Dana-Farber Cancer Institute. He is also an Associate Professor of Medicine at Harvard Medical School.
Dr. Krop is a translational investigator focused on the development of novel molecularly targeted therapies and immunotherapies for breast cancer, and elucidating the mechanisms of resistance to these treatments. The majority of his effort is concentrated in the area of HER2+ breast cancer. He was a leader in the development of the antibody-drug conjugate trastuzumab emtainsine (T-DM1).
Dr. Krop is a member of the National Cancer Institute’s Breast Cancer Steering Committee and co-chairs its Immuno-Oncology Working Group. He is also the co-vice chair for correlative science for the Alliance for Clinical Trials in Oncology. He is a member of the Eastern Cooperative Oncology Group Data Monitoring Committee, and is co-chair of the HER2-working group of the Translational Breast Cancer Research Consortium.
Dr. Krop is a graduate of Johns Hopkins University and Johns Hopkins University School of Medicine. He trained at Johns Hopkins Hospital, Dana-Farber Cancer Institute, Harvard Medical School, and Brigham and Women’s Hospital. He completed a medical oncology fellowship at Dana-Farber.