Chugai Submits Application in Japan to Expand Use of FoundationOne CDx as Companion Diagnostic for Rozlytrek in ROS1 Fusion-Positive NSCLC

September 08, 2019 /BioonBIOON/ -- Chugai Pharmaceutical, a Japanese pharmaceutical company controlled by Swiss pharmaceutical giant Roche, recently announced that it has submitted an application to the Japanese Ministry of Health, Labour and Welfare (MHLW) to expand the FoundationOne® CDx Cancer Genomic Profile (hereinafter referred to as “F1CDx”).”, cancer genomic analysis testing) as a companion diagnostic for the targeted anticancer drug Rozlytrek (entrectinib) 100 mg and 200 mg capsules in the treatment of patients with ROS1 fusion-positive non-small cell lung cancer (NSCLC)DiagnosisKit. On March 15 this year, Chugai Pharmaceutical submitted regulatory application documents to the MHLW for Rozlytrek in the treatment of ROS1 fusion-positive NSCLC patients, and the application is currently under review.

F1CDx is a test based on developed by Foundation Medicine, a cancer diagnostics company under Roche.In Vitro DiagnosticsThe device’s next-generation sequencing product utilizes DNA isolated from patient tumor tissue to detect and analyze substitutions, insertions, and deletions across 324 genes, selected gene rearrangements, as well as microsatellite instability (MSI) andTumorGenomic signatures, including tumor mutational burden (TMB). As a comprehensive auxiliaryDiagnosisFunction: As of now, this kit has been approved in Japan for use as a companion diagnostic for 14 molecular targeted drugs.Diagnosis。

This submission aims to expand the intended use of this diagnostic product as a companionDiagnosisTest Kit: Utilizing next-generation sequencing to detect ROS1 gene fusions, this kit identifies patients with ROS1 fusion-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) who are most likely to benefit from Rozlytrek treatment. ROS1 fusion genes are abnormal genes formed by chromosomal translocations that fuse the ROS1 gene with other genes (such as CD74). The ROS1 fusion kinases produced by these genes are believed to promote cancer cell proliferation. ROS1 fusion genes are present in approximately 1–2% of NSCLC cases, with higher expression observed in adenocarcinomas.

Rozlytrek is a ROS1/TRK inhibitor that received approval from the MHLW on June 18 this year for the treatment of adult and pediatric patients with advanced, recurrent NTRK fusion-positive solid tumors. This drug is a novel "broad-spectrum" anticancer agent and is the first tumor-agnostic therapy approved in Japan targeting NTRK gene fusions (i.e., independent ofTumortumor-agnostic) drugs. NTRK gene fusions have been identified in a range of hard-to-treat solid tumor types, including pancreatic cancer, thyroid cancer, and salivary gland cancer,Breast Cancer, colorectal cancer and lung cancer. NTRK gene fusionBiomarkersTesting is the only method to determine which patients may be eligible for treatment with Rozlytrek.

In late June this year, FoundationOne® CDx Cancer Genomic Profile was approved for the first time in Japan, marking the first next-generation sequencing product based on pan-tumor companion diagnostics to be approved in Japan, as a companion diagnostic for Rozlytrek.DiagnosisTest kit, by detectingTumorNTRK fusion genes (fusions involving NTRK1, NTRK2, NTRK3, and other genes), thereby identifying target patients suitable for Rozlytrek treatment.

The active pharmaceutical ingredient of Rozlytrek is entrectinib, an oral, selective tyrosine kinase inhibitor (TKI) indicated for the treatment of locally advanced or metastatic solid tumors harboring NTRK1/2/3 (encoding TRKA/TRKB/TRKC) or ROS1 gene fusions. Entrectinib can cross the blood-brain barrier and inhibit the kinase activity of TRKA/B/C and ROS1 proteins, leading to the death of cancer cells with ROS1 or NTRK gene fusions. Entrectinib demonstrates efficacy against both primary and metastatic central nervous system (CNS) diseases, without adverse off-target activity. Currently, Roche is investigating the potential of entrectinib in the treatment of various solid tumors, including non-small cell lung cancer (NSCLC), pancreatic cancer, sarcoma, thyroid cancer, salivary gland cancer, gastrointestinal stromal tumors (GIST), and cancer of unknown primary (CUP).

In the United States, Rozlytrek was approved on August 15, 2019FDAApproval: (1) for the treatment of pediatric and adult patients aged 12 years and older with advanced solid tumors harboring NTRK fusions; (2) for the treatment of adult patients with ROS1-positive metastatic non-small cell lung cancer (NSCLC). In the European Union, the European Medicines Agency (EMA) had previously granted Rozlytrek Priority Medicines (PRIME) status. Previously, Rozlytrek had been granted Breakthrough Therapy Designation (BTD) in the United States, Priority Medicines (PRIME) status in the European Union, SAKIGAKE designation (for innovative drugs) in Japan, and orphan drug designation.

It is particularly worth mentioning that Rozlytrek isFDAThe third approved pan-tumor therapy based on different tumor typesBiomarkersrather than anticancer drugs based on the tissue type of tumor origin, marking a new paradigm in “tumor-agnostic” (i.e., independent of tumor type) cancer drug development. The agency’s previously approved “Tumor“Agnostic” indications include: In May 2017, the FDA approved Merck’s Keytruda (pembrolizumab) for the treatment of pediatric and adult patients with microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR) solid tumors; in December 2018, approval was grantedBayerVitrakvi (larotrectinib) for the Treatment of Advanced Solid Tumors with NTRK Gene Fusions in Children and Adults. (Bioon.com)

Original Source:Chugai Files for Expanded Use of FoundationOne CDx Cancer Genomic Profile as a Companion Diagnostic of Rozlytrek for ROS1-Positive NSCLC