▎WuXi AppTec Content Team Report

On October 27, the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) announced that Roche (Roche) had submitted an application.Alectinib Hydrochloride CapsulesProposed inclusion in the breakthrough therapy category, with the proposed indication for use.Anaplastic Lymphoma Kinase (ALK)Adjuvant Treatment for Patients with Positive Non-Small Cell Lung Cancer (NSCLC) After Surgery。

Screenshot source: CDE

Lung cancer is one of the most common cancers globally, with NSCLC accounting for approximately 85% of lung cancer cases. For patients with ALK-positive NSCLC, especially those in the early stages, delaying disease progression is particularly important. This is because this group tends to be relatively younger, averaging about 55 years old, and also because they are more prone to brain metastases compared to other types of NSCLC. Once the disease recurs, it usually spreads to other parts of the body, at which point it is generally considered incurable.

Alectinib is a new generation ALK inhibitor developed by Roche. It was previously approved for marketing in China in 2018 for the treatment of ALK-positive locally advanced or metastatic NSCLC. The application proposed by the CDE for inclusion in the breakthrough therapy category this time targets a new indication:For the adjuvant treatment of ALK-positive NSCLC patients after surgery。

It is worth mentioning that, on October 18, 2023, Roche just announcedAlectinib Achieves Primary Endpoint in Global Phase 3 ALINA StudyThe ALINA study is a Phase 3, randomized, active-controlled, multicenter, open-label study aimed at patients with completely resected Stage IB (tumor ≥4cm) to Stage IIIA (UICC/AJCC 7th edition) ALK-positive NSCLC.Evaluate the efficacy and safety of Alectinib compared to platinum-based chemotherapy in adjuvant treatmentThis study enrolled 257 patients. The primary endpoint was disease-free survival (DFS). Secondary endpoints included overall survival (OS), time to central nervous system (CNS) recurrence or death, and safety. The study data were presented as a key study in an oral report during the Presidential Symposium session at the 2023 European Society for Medical Oncology (ESMO) Congress.

The ALINA study results show that, compared with the platinum-based chemotherapy group, adjuvant treatment with Alectinib for completely resected IB (tumor ≥4 cm) to IIIA stage ALK-positive NSCLC patients...Can reduce the risk of disease recurrence or death in patients by 76%。

At the same time, the current research results also observed a clinically significant improvement in CNS-DFS (HR = 0.22). In this analysis, the median DFS in the alectinib group has not yet been reached (NE), while the median DFS in the chemotherapy group was 41.3 months; the OS data for patients receiving alectinib as adjuvant therapy in the ALINA study is not yet mature and relevant data will be released after longer follow-up.

In this study, the safety and tolerability profile of Alectinib was consistent with previous studies, with no new unexpected safety signals observed. The incidence of grade 3 or 4 adverse events (AEs) was 30% in the Alectinib group and 31% in the chemotherapy group. No grade 5 adverse events were observed in either treatment group. In the Alectinib group, 5.5% of patients discontinued treatment due to adverse events, compared to 12.5% in the chemotherapy group.

ALINA Principal Investigator Professor Wu Yilong from Guangdong Provincial People's Hospital once stated in a press release: "ALKPatients positive for mutations respond well to ALK-TKI treatment and achieve long-term survival benefits; therefore,ALKGene mutations are also known as 'diamond mutations.' Although early-stage patients receive adjuvant chemotherapy after surgery, nearly half of them will still experience recurrence. Against this backdrop,Global scholars jointly conducted the ALINA study, in which China contributed the second-largest number of patients., which also embodies the efforts of Chinese scholars.This study heralds the shift of ALK-TKI treatment from advanced stages to earlier stages, which may completely transform the current treatment landscape for the ALK-positive early-stage NSCLC population.。”

[1] Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China. Retrieved Oct 27, 2023. From https://www.cde.org.cn/main/xxgk/listpage/2f78f372d351c6851af7431c7710a731

[2] ALINA Study Data Released: Alectinib Reduces Risk of Disease Recurrence or Death by 76% in ALK-Positive Early-Stage Non-Small Cell Lung Cancer Patients. Retrieved Oct 18 , 2023. From https://mp.weixin.qq.com/s/c1GUv0ZpVBnVkVCd9Q_gNg