Yale School of Medicine New Haven, Connecticut
Chief Clinical Research Officer Associate Cancer Center Director, Clinical Research Director, Clinical Trials Office Yale Cancer Center
Improving HER2 testing so that more patients can benefit from HER2-targeted therapy.
Twenty percent of breast cancers express a very high level of a protein called HER2. These HER2-positive cancers are treated with drugs targeting HER2, which can be highly effective. The level of HER2 is measured using an IHC test and categorized as 0, 1+, 2+ or 3+. Only cancers with the highest level of HER2 protein, 3+, are called HER2-positive. Cancers that are HER2 IHC 1+ or 2+ are termed HER2-low and have intermediate levels of HER2 protein expression between HER2-positive and HER2 IHC 0 cancers. Most current anti-HER2 drugs, such as trastuzumab (Herceptin), are not effective in HER2-low cancers. However, the development of more potent HER2 drugs such as trastuzumab deruxtecan (T-DXd, Enhertu) is changing this paradigm. T-DXd recently demonstrated a high level of effectiveness in HER2-low breast cancers and is the only drug the FDA has approved to treat HER2-low cancers. Because up 50 percent of all breast cancers have some level of HER2, the potential clinical impact of T-DXd in breast cancer is large. However, the HER2 test was designed to detect high HER2 levels, not low, and it is not accurate at distinguishing HER2-low cancers from HER2 0. In fact, 30 percent of HER2 0-classified cancers responded to T-DXd in clinical trials, further suggesting that the current test misses many T-DXd-responsive cancers.
Dr. Krop has developed a new HER2 test optimized for the HER2-low expression range that could more accurately distinguish patients who may benefit from T-DXd. To analyze this new test, Dr. Krop is conducting a clinical trial of T-DXd in 50 patients with HER2 0 metastatic breast cancer. He and his team will use the new HER2 IHC test on trial participant samples and determine if it is able to predict the cancers that respond versus those that did not.
Ian Elliott Krop, MD, PhD, is the Chief Clinical Research Officer and Associate Cancer Center Director for Clinical Research at Yale Cancer Center in New Haven, CT.
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 emtansine (T-DM1).
Dr. Krop currently serves as Chief Scientific Officer for the Translational Breast Cancer Research Consortium. He 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.
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.
2017
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