- The most commonly reported adverse reactions included fatigue, constipation, dysgeusia, edema, dizziness, diarrhea, nausea, dysesthesia, dyspnea, pain, anemia, cognitive disorders, weight increase, vomiting, cough, blood creatinine increase, joint pain, fever and muscle pain.

[Reference information]
Media release issued by Chugai on December 19, 2018
Title: Chugai Files a New Drug Application for a ROS1/TRK Inhibitor Entrectinib for the Treatment of NTRK Fusion-Positive Solid Tumors
https://www.chugai-pharm.co.jp/english/news/detail/20181219170000_579.html

About Rozlytrek
Rozlytrek is an oral tyrosine kinase inhibitor that blocks ROS1 (c-ros oncogene 1) and TRK (neurotrophin receptors) family strongly and selectively. It blocks ROS1 and TRK kinase activity, and inhibits proliferation of cancer cells with ROS1 or NTRK gene fusions. Rozlytrek has been granted Breakthrough Therapy Designation by the U.S. Food and Drug Administration and Priority Medicines designation by the European Medicines Agency for the treatment of NTRK fusion gene positive, locally advanced or metastatic solid tumors in adult and pediatric patients who have either progressed following prior therapies or have no acceptable standard therapies. FDA has granted priority review for Rozlytrek for the treatment of NTRK fusion-positive solid tumors and ROS1 fusion-positive non-small cell lung cancer (NSCLC). In Japan, Chugai filed an application for approval of ROS1 fusion gene positive NSCLC in March 2019.

About NTRK fusion gene positive cancer
NTRK fusion gene is an abnormal gene that can be formed by fusing the NTRK genes (NTRK1, NTRK2, NTRK3 encode TRKA, TRKB, TRKC protein, respectively) and other genes (ETV6, LMNA, TPM3, etc.) as a result of chromosomal translocation^1-3). The TRK fusion kinase made from NTRK fusion gene is thought to promote cancer cell proliferation. There is very rare expression of NTRK fusion but in various adult and pediatric solid tumors, including infantile fibrosarcoma, glioma, glioblastoma, diffuse intrinsic pontine glioma (DIPG), congenital mesoblastic nephroma, melanoma, inflammatory myofibroblastic tumor (IMT), uterus sarcoma, soft tissue tumor, gastrointestinal stromal tumor (GIST), secretory carcinoma of breast, secretory carcinoma of salivary gland, cancer of unknown primary, lung cancer, colorectal cancer, appendiceal cancer, breast cancer, gastric cancer, ovarian cancer, thyroid cancer, cholangiocarcinoma, pancreatic cancer, head and neck cancer, and various sarcomas.

Trademarks used or mentioned in this release are protected by law.

1. Martin-Zanca D, Hughes SH, Barbacid M. A human oncogene formed by the fusion of truncated tropomyosin and protein tyrosine kinase sequences. Nature 1986; 319(6056): 743-8.
2. Martin-Zanca D, Oskam R, Mitra G, Copeland T, Barbacid M. Molecular and iochemical Characterization of the Human trk Proto-Oncogene. Molecular and Cellular Biology 1989; 9(1): 24-33.
3. Lange AM, Lo HW. Inhibiting TRK Proteins in Clinical Cancer Therapy. Cancers 2018; 10: 105.