Chugai Launches Rozlytrek, Japan's First Tumor-Agnostic Therapy for NTRK Fusion-Positive Solid Tumors

September 05, 2019 News /BioonBIOON/ -- Chugai Pharmaceutical, a Japanese pharmaceutical company controlled by Swiss pharmaceutical giant Roche, recently announced the launch of Rozlytrek (entrectinib) 100 mg and 200 mg capsules in the Japanese market. This targeted anticancer drug, an anticancer agent/tyrosine kinase inhibitor, is indicated for the treatment of adult and pediatric patients with advanced or recurrent solid tumors harboring neurotrophic tyrosine receptor kinase (NTRK) fusions. In Japan, Rozlytrek was approved on June 18, 2019, and was included in the National Health Insurance (NHI) reimbursement price list on September 4.

Rozlytrek is a medication that enables advancements in personalized medicine, one of the goals set by Chugai Pharmaceutical. After receiving Sakigake designation (for innovative drugs) from Japan’s Ministry of Health, Labour and Welfare (MHLW) for the treatment of NTRK fusion-positive advanced/recurrent solid tumors (with extremely rare genetic mutations), Chugai Pharmaceutical obtained the world’s first regulatory approval for Rozlytrek in Japan on June 18, 2019.

Rozlytrek is a novel “broad-spectrum” anticancer drug and the first tumor-agnostic (i.e., independent ofTumortype-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. Currently, another New Drug Application for Rozlytrek is under review by Japanese regulatory authorities for the treatment of patients with ROS1 fusion-positive locally advanced or metastatic non-small cell lung cancer (NSCLC).

In other countries, Rozlytrek is approved by the U.S.FDAGranted Breakthrough Therapy designation and approved on August 15, 2019: (1) for the treatment of pediatric and adult patients aged 12 years and older with NTRK fusion-positive advanced solid tumors; (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.

For NTRK gene fusion biomarker testing, Chugai Pharmaceutical received approval from the Japanese MHLW on June 26, 2019, for FoundationOne® CDx Cancer Genomic Profile as a companion diagnostic for Rozlytrek.DiagnosisKit.It is worth mentioning that this product is the first pan- based therapy approved in JapanTumorAccompanied byDiagnosisNext-generation sequencing products.

FoundationOne® CDx Cancer Genomic Profile is a test developed by Foundation Medicine, a Roche company, based onIn 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 auxiliary diagnostic tool, this kit can serve as an adjunct for certain molecular targeted drugs approved in Japan.Diagnosis。

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).

FDAThe approval of Rozlytrek is based on data from multiple clinical studies, including the pivotal Phase II study STARTRK-2, the Phase I study STARTRK-1, the Phase I study ALKA-372-001, and the Phase I/II study STARTRK-NG conducted in pediatric patients. In a pooled analysis, the efficacy of Rozlytrek across various solid tumor types was evaluated. The results showed:

——Treatment of NTRK fusion-positive solid tumors (n=54): The overall response rate (ORR) for Rozlytrek was 57%, with a complete response rate (CR) of 7.4%. Objective responses to Rozlytrek were observed across 10 different types of solid tumors, and the median duration of response (DoR) was 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%.

——Treatment of ROS1-positive metastatic NSCLC (n=51): The overall response rate (ORR) for Rozlytrek was 78%, with 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 particularly worth mentioning that Rozlytrek isFDAThe third approved therapy based on commonalities across different tumor typesBiomarkersrather than anticancer drugs based on the tissue of origin of the tumor, 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 U.S. 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, it was approvedBayerVitrakvi (larotrectinib) for the treatment of advanced solid tumors with NTRK gene fusions in pediatric and adult patients. In clinical studies, Vitrakvi demonstrated an overall response rate (ORR) of 75% in patients with NTRK fusion-positive solid tumors, including a complete response rate (CR) of 22%. (Bioon.com)

Original Source:Chugai Launches Rozlytrek, an Anticancer Agent for the Treatment of NTRK Fusion-Positive Solid Tumors