Chentech Pharmaceuticals/AstraZeneca's Class 1 New Drug Zorifertinib Approved in China for First-Line Treatment of NSCLC with CNS Metastases

On November 20, the NMPA announced that Alpha Biopharma/AstraZeneca's Class 1 new drug, Zorifertinib Hydrochloride Tablets, has been approved for marketing in China. This medication is indicated for patients with epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations.First-line treatment for adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) accompanied by central nervous system (CNS) metastases.（CXHS2300019/20）。

Screenshot source: NMPA official website

Zolitinib（Zorifertinib，AZD3759）Originally developed by AstraZeneca.In January 2018, Alpha Biopharma partnered with AstraZeneca to advance the Phase II and III clinical development of Zorifertinib.

EGFR Sensitivity Mutation(Exon 19Del and L858R mutations are the most common)It is most common in NSCLC patients, accounting for approximately 30%. Central nervous system (CNS) metastasis is a common metastatic site in EGFR mutation-positive NSCLC, with 40%-60% of EGFR-sensitive mutant NSCLC developing brain metastases during disease progression. Due to the blood-brain barrier increasing the difficulty of drug penetration into the brain, the treatment of advanced EGFR-sensitive mutant NSCLC with CNS metastases faces significant challenges.

Zorifertinib is an effective, orally administered, reversible EGFR activating mutation (L858R and Exon 19Del) tyrosine kinase activity inhibitor, specifically designed for the treatment of advanced NSCLC patients with central nervous system metastases. Unlike other TKI drugs, Zorifertinib is not a substrate for the blood-brain barrier endothelial cell transport proteins P-gp and BCRP.With the ability to fully penetrate the blood-brain barrier, it can maintain high drug exposure in brain tissue and cerebrospinal fluid.Preclinical and early clinical data show that zorifertinib has a blood-brain barrier penetration rate of up to 100%.

The approval of Zorifertinib was based on the positive results of the II/III clinical study EVEREST (NCT03653546). This study is a randomized, open-label, international multicenter clinical trial and also the world's first large-scale prospective international multicenter clinical trial targeting EGFR mutation-positive NSCLC patients with central nervous system metastases.

Research results presented at the 2023 ASCO Annual Meeting show:Compared with first-generation EGFR TKIs (gefitinib or erlotinib), zorifertinib as a first-line treatment demonstrated superior intracranial and systemic antitumor activity in patients with advanced NSCLC harboring EGFR-sensitizing mutations and central nervous system metastases.. Overall anti-tumor effectThe data is:

• Median in the Zorifertinib groupPFS reached 9.6 months (vs Control group 6.9 months), reducing the risk of disease progression or death by 28%;

• The ORR in the Zoritini group was 68.6% (vs 58.4% in the control group).；

• Zorifertinib GroupThe median DoR was 8.2 months (vsControl group 6.8 months)。

Screenshot source: Insight database

In terms of control of brain metastases, the zoritini group showed better intracranial PFS, ORR, and DoR compared to the control group.。

As assessed by BICR:Zorifertinib vs Control GroupMedian PFS was 15.2 months vs 8.3 months, ORR was 75.0% vs 64.2%, and DoR was 12.4 months vs 7.0 months.

In terms of safety, the incidence of TRAEs of any grade was similar between the zolitinib treatment group and the control group (97.7% vs. 94.0%), with the incidence of Grade ≥3 TRAEs being 65.9% and 18.3%, respectively. No new safety signals were identified in the study.

The approval of Zorifertinib will provide a new option for the first-line treatment of advanced EGFR-sensitive mutant NSCLC with central nervous system (CNS) metastases.

Cover Source:ZCOOL Hello Plus

Disclaimer:This article is for information sharing only and does not represent the position or viewpoint of Insight. It does not recommend or introduce any treatment plans. If you have any needs, please consult and contact正规医疗机构.

Editor：vvy

PR Article Coordination: WeChat insightxb

SubmissionWeChat: insightxb; Email: insight@dxy.cn

Diversified functions, traceable data……

Insight Database Web Version Awaits Your Experience

Click to read the original text,ImmediatelyUnlock！