Entrectinib (ROZLYTREK®) Gains New Indication in China for ROS1-Positive NSCLC, Offering Long-Term Survival Hope

On August 15, 2022, Roche Pharma China announced today that the National Medical Products Administration (NMPA) of China has officially approved Roche's targeted anticancer drug, Rozlytrek.^®(English trade name: ROZLYTREK, Chinese-English generic name: 恩曲替尼/Entrectinib) is used to treat adult patients with ROS1-positive locally advanced or metastatic non-small cell lung cancer (hereinafter referred to as NSCLC).

This is Roche^®Less than two weeks after being approved on July 29 for the treatment of patients with NTRK fusion gene-positive solid tumors, the second indication was approved in China.

As of the approval date, entrectinib is the first ROS1 inhibitor approved in China with demonstrated efficacy in the central nervous system (CNS).，Expected to fill the treatment gap in a specific field of lung cancer, bringing new hope for long-term survival to Chinese ROS1-positive NSCLC patients.

Chinese ROS1-Positive Lung Cancer Patients Face Significant Unmet Clinical Needs

According to the national cancer statistics released by the National Cancer Center in 2022, the incidence and mortality rates of lung cancer in China rank first. In 2016 alone, there were over 82....810,000 people are diagnosed with lung cancer, of which non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases.

ROS1 is a receptor tyrosine kinase encoding gene, structurally similar to anaplastic lymphoma kinase (ALK), and is a rare driver gene identified in NSCLC. The incidence rate in the Chinese population ranges between 1-3%, with fusion (rearrangement) being the primary type of variation in the ROS1 gene. Among patients with ROS1 fusion-positive NSCLC, up to 40% have been found to have central nervous system (CNS) metastases at the time of diagnosis.

Entrectinib is a potent and selective inhibitor targeting pan-TRK and ROS1 tyrosine kinases, with central nervous system (CNS) activity. It can cross the blood-brain barrier and induce cell death in ROS1-positive or NTRK-positive cancer cells by blocking the activity of ROS1 and NTRK kinases.

A New Generation of Targeted Precision Therapy Sheds New Light on ROS1-Positive Patients

The National Medical Products Administration (NMPA) approved entrectinib for the treatment of ROS1-positive NSCLC patients this time, mainly based on three Phase I/II clinical studies (ALKA-372-001, STARTRK-1, STARTRK-2).  The results of the pooled analysis. The study results showed that regardless of the presence or absence of central nervous system (CNS) metastases, the data for entrectinib demonstrated efficacy.

Based on the data update from the 2022 World Conference on Lung Cancer (WCLC), in the first-line treatment of ROS1-positive NSCLC patients, entrectinib demonstrated an overall objective response rate (ORR) of 68.7%, a median duration of response (DOR) of 35.6 months, a median progression-free survival (PFS) of 17.7 months, and a median overall survival (OS) of 47.7 months. Meanwhile, entrectinib showed excellent brain protection effects: the risk of intracranial metastasis after 12 months of entrectinib treatment was only 1%; furthermore, the intracranial objective response rate (IC-ORR) for patients with measurable brain metastases at baseline reached 80.0%, demonstrating intracranial anti-tumor efficacy, and the drug was safe and tolerable.

In recent years, significant progress has been made in the treatment of rare genetic mutations, bringing tangible benefits to patients and driving the long-term development of therapies targeting rare mutations. As the principal investigator of the global clinical study STARTRK-2 for entrectinib, Professor Lu Shun from Shanghai Chest Hospital, affiliated with Shanghai Jiao Tong University, stated: "Currently, the options for ROS1-targeted therapies in China are relatively limited, and there are still many unmet needs in clinical practice. The approval of the new generation ROS1 inhibitor entrectinib provides a new treatment option for Chinese patients with ROS1-positive NSCLC."

As China’s clinical research level continues to improve, Chinese clinical trials are gradually aligning with international standards, enabling more innovative drugs to accelerate their market entry in China and providing Chinese patients with cutting-edge treatment options synchronized globally. Regarding the recent approval of Entrectinib in China, Professor Fan Yun from the Cancer Hospital of the University of Chinese Academy of Sciences commented: “Entrectinib has demonstrated consistent therapeutic benefits in the Chinese population as seen globally, offering more treatment options for Chinese ROS1-positive patients.”     "And drug accessibility. We hope that such innovative drugs can enter China quickly in the future, adding another powerful tool for clinical cancer treatment."

Benefiting Chinese Patients, Supporting Healthy China 2030

2019YearIn August, the U.S. FDA approved entrectinib for the treatment of ROS1-positive metastatic non-small cell lung cancer (NSCLC), marking the first FDA-approved selective therapy targeting both ROS1 and NTRK. Currently, the latest guidelines both in China and internationally have included entrectinib in their recommended regimens. The 2022 V3 edition of the NCCN Non-Small Cell Lung Cancer (NSCLC) Guidelines has listed entrectinib as the first-line preferred treatment for ROS1-positive NSCLC.

Li Xin, Head of Roche Global Pharma Development China Center, stated: "The approval of Entrectinib for the treatment of ROS1-positive non-small cell lung cancer patients will bring longer survival hope to Chinese ROS1-positive non-small cell lung cancer patients. In the future, Roche will continue to invest in R&D in the field of lung cancer, striving to make continuous breakthroughs in the treatment of more rare target mutations in lung cancer, benefiting more lung cancer patients."

President of Roche Pharma China, Bian Xin, stated: "In just two weeks after the approval of the NTRK indication, Entrectinib (Rozlytrek)..."^®) The approval of the ROS1 indication by the Chinese government will bring longer survival to patients with ROS1-positive non-small cell lung cancer and significantly reduce the risk of brain metastases. Roche will continue to uphold the principle of 'acting on patients' needs first', keep pace with the times, introduce more innovative products to China faster to meet the unmet needs of Chinese cancer patients, and also express gratitude for Roche's support.^®"Patients, medical professionals, and relevant government departments who have made significant contributions."

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