Roche's Tumor-Agnostic Small Molecule Targeted Therapy Entrectinib Nominated for Priority Review in China

On October 28, information on the website of the Center for Drug Evaluation (CDE) under China's National Medical Products Administration (NMPA) indicated that Roche's marketing application for entrectinib capsules is proposed to be included in the priority review. It will be processed under the priority review program in accordance with the priority review scope "(V) Drugs eligible for conditional approval." The indication for which marketing approval is sought for entrectinib capsules is "NTRK fusion-positive locally advanced or metastatic solid tumors."

Screenshot source: CDE official website

NTRK fusion-positive tumors arise from the fusion of neurotrophic tyrosine receptor kinase (NTRK) genes (NTRK1/2/3) with other genes, resulting in aberrant TRK proteins (TRKA/TRKB/TRKC) that activate signaling pathways associated with the proliferation of specific cancers. NTRK gene fusions may occur in tumors originating from diverse anatomical sites, including breast cancer, cholangiocarcinoma, colorectal cancer, neuroendocrine carcinoma, non-small cell lung cancer (NSCLC), pancreatic cancer, and others. TRK fusions can be detected through a range of diagnostic assays, including fluorescence in situ hybridization (FISH) and quantitative polymerase chain reaction (RT-PCR), among others.

Entrectinib is a highly selective tyrosine kinase inhibitor designed to target NTRK and ROS1 gene fusions, capable of inhibiting TRK A/B/C and ROS1 kinase activity. In August 2019, the U.S. FDA granted accelerated approval for its use in treating patients with advanced or recurrent solid tumors harboring NTRK gene fusions. The FDA's approval was based on results from multiple clinical trials, which demonstrated that this tumor-agnostic precision oncology therapy achieved an objective response rate (ORR) of 57.4% in patients with NTRK fusion-positive solid tumors, with a median duration of response (DOR) of 10.4 months. Patients with up to 10 different types of solid tumors responded to this therapy. Notably, in patients with solid tumors that had metastasized to the brain, Rozlytrek achieved an intracranial objective response rate of 54.5%, with one-quarter of responding patients achieving a complete response.

In August 2019, the FDA simultaneously approved entrectinib for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) harboring ROS1 gene mutations. Clinical trial results demonstrated that among 51 ROS1-positive NSCLC patients, the overall response rate reached 78%, and the complete response rate reached 5.9%. Among the 40 patients who experienced tumor shrinkage, 55% had a duration of response exceeding 12 months.

References:

[1] Detailed Information on Priority Review Public Notice. Retrieved 2021-10-28, from https://www.cde.org.cn/main/xxgk/listpage/9f9c74c73e0f8f56a8bfbc646055026d

(Original text abridged)

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