• First approved next generation sequencing based pan-tumor companion diagnostic in Japan
• Enables physicians to identify patients who will likely benefit from Rozlytrek by detecting NTRK gene fusions
• Very rare occurrence of NTRK fusion in various adult and pediatric solid tumors and sarcomas

TOKYO, June 27, 2019 -- Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) announced that the Ministry of Health Labour and Welfare (MHLW) granted an additional approval for FoundationOne^® CDx Cancer Genomic Profile as a companion diagnostic for Rozlytrek^® (entrectinib) for the treatment of neurotrophic tyrosine receptor kinase (NTRK) fusion positive solid tumors on June 26, 2019. The approval enables FoundationOne CDx Cancer Genomic Profile to be used as a companion diagnostic for Rozlytrek by detecting NTRK fusion genes (fusion genes between NTRK1, NTRK2, NTRK3 and other genes). Rozlytrek is a ROS1/TRK inhibitor and was approved for the treatment of adult and pediatric patients with NTRK fusion positive advanced and recurrent solid tumors on June 18, 2019.

“The conventional concept of cancer treatment focuses on the site where the cancer started. However, it is drastically changing with the emergence of a completely new approach called tumor agnostic treatment; an approach which targets genomic mutations that drive cancers instead of the tumor location in the body. We are proud of the MHLW approval of FoundationOne CDx Cancer Genomic Profile as a companion diagnostic for Rozlytrek which represents this new tumor agnostic treatment approach,” said Dr. Minoru Watanabe, Chugai’s Vice President, Head of Foundation Medicine Unit. “A comprehensive genomic profiling test is especially beneficial in identifying rare gene mutations expressed in multiple cancer types, including NTRK gene fusions. Chugai will further strive to provide services to help physicians’ swift and appropriate decision making in order to realize patient-centric healthcare.”

Developed by Foundation Medicine Inc., FoundationOne CDx Cancer Genomic Profile is a next-generation sequencing based in vitro diagnostic device for the detection and analysis of substitutions, insertion and deletion alterations, and copy number alterations in 324 genes and select gene rearrangements, as well as genomic signatures including microsatellite instability (MSI) and tumor mutational burden (TMB) using DNA isolated from patient’s tumor tissues. As a comprehensive companion diagnostic function, it can be also used as a companion diagnostic for certain molecular-targeted drugs approved in Japan.

As a leading company in the field of oncology, Chugai is committed to realize advanced personalized oncology care and contribute to patients and healthcare providers through comprehensive genomic profiling.

Approval information The underlined part has been newly added.

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.

[References]

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.