Chugai Secures Japanese Approval for Rozlytrek as a New Treatment for ROS1 Fusion-Positive Non-Small Cell Lung Cancer

February 22, 2020 News /BioonBIOON/ -- Chugai Pharmaceutical, a Japanese pharmaceutical company controlled by Roche, recently announced that the Ministry of Health, Labour and Welfare (MHLW) of Japan has approved a new indication for the targeted anticancer drug Rozlytrek (entrectinib) for the treatment of adult patients with ROS1 fusion-positive, unresectable, advanced or metastatic non-small cell lung cancer (NSCLC). ROS1 fusion genes are abnormal genes formed by chromosomal translocation, which fuse the ROS1 gene with other genes (such as CD74). The ROS1 fusion kinase expressed by these genes is believed to promote the proliferation of cancer cells. ROS1 fusion genes are found in 1-2% of NSCLC patients, with a higher prevalence in adenocarcinoma.

Rozlytrek is an anticancer agent/tyrosine kinase inhibitor that received the world’s first regulatory approval in Japan in June 2019 for the treatment of adult and pediatric patients with advanced or recurrent neurotrophic tyrosine receptor kinase (NTRK) fusion-positive solid tumors. Rozlytrek is a “broad-spectrum” anticancer drug and the first tumor-agnostic (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.

This approval was primarily based on the results of the open-label, multicenter, global Phase II STARTRK-2 study. Conducted in patients with ROS1-positive metastatic non-small cell lung cancer (NSCLC) (n=51), the study demonstrated an overall response rate (ORR) of 78% and a complete response rate (CR) of 5.9% with Rozlytrek treatment. Among the 40 patients who achieved a response, 55% had a duration of response ≥12 months.

FoundationOne® CDx Cancer Genomic Profile, a next-generation sequencing product developed by Foundation Medicine, a cancer diagnostics company under Roche, is used as a companion diagnostic for Rozlytrek.DiagnosisProduct for identifying cancer patients who may benefit from Rozlytrek treatment, including: patients with ROS1 fusion-positive unresectable advanced or metastatic NSCLC, and patients with NTRK fusion-positive advanced or recurrent solid tumors.

Dr. Osamu Okuda, Executive Vice President and Co-Head of the Project and Lifecycle Management Department at Chugai Pharmaceutical, stated, “We are delighted to announce the approval of Rozlytrek for the treatment of adult patients with ROS1 fusion-positive non-small cell lung cancer (NSCLC). Launched last year as Chugai Pharmaceutical’s inaugural product, this medication is designed to provide advanced personalized healthcare to patients with NTRK fusion-positive solid tumors, regardless of patient age orTumorregardless of its origin. ROS1 is an important cancer driver gene, found in 1-2% of NSCLC patients. Rozlytrek will provide a new treatment option for ROS1 fusion-positive NSCLC patients. We will continue to strive and contribute to the development of advanced personalized medicine.”

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 and lacks adverse off-target activity. Currently, Roche is investigating the potential of entrectinib in treating 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 in August 2019 by the U.S.FDAApproval: (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). Clinical study results showed: (1)In the treatment of NTRK fusion-positive solid tumors (n=54), Rozlytrek demonstrated an overall response rate (ORR) of 57% and a complete response rate (CR) of 7.4%. Objective responses to Rozlytrek were observed across 10 different types of solid tumors, with a median duration of response (DoR) of 10.4 months (range: 2.8–26.0 months). Among the 31 patients who achieved a response, 61% had a duration of response ≥9 months. Importantly, therapeutic responses to Rozlytrek were also observed in patients with baseline central nervous system (CNS) metastases, with an intracranial response rate of 50%. (2)For the treatment of ROS1-positive metastatic NSCLC (n=51), Rozlytrek demonstrated an overall response rate (ORR) of 78% and a complete response rate (CR) of 5.9%. Among the 40 patients who achieved a response, 55% had a duration of response ≥12 months.

It is worth mentioning that Rozlytrek is the United StatesFDAThe third approved pan-tumor indication based on different tumor typesBiomarkersrather than anticancer drugs based on the tissue of tumor origin, marking a new paradigm in “tumor-agnostic” (i.e., independent of tumor type) cancer drug development. Previously approved “tumor-agnostic” indications by the agency include: the 2017 approval of Merck’s Keytruda (pembrolizumab) for the treatment of microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR)Tumor, approved in 2018BayerVitrakvi (larotrectinib) for the Treatment of NTRK Gene FusionsTumor. In clinical studies, the overall response rate (ORR) of Vitrakvi for the treatment of NTRK gene fusion solid tumors was 75%, with a complete response rate (CR) of 22%. (Bioon.com)

Original Source:Chugai Obtains Approval for Additional Indication of Rozlytrek for ROS1 Fusion-Positive Non-Small Cell Lung Cancer