▎WuXi AppTec Content Team Report

On October 8, the official website of the Center for Drug Evaluation (CDE) of the China National Medical Products Administration (NMPA) announced that AstraZeneca's Class 1 new drug AZD9592 had been granted two clinical trial implied permissions, with the indications being:In Combination with Osimertinib for the Treatment of Advanced Solid Tumors; In combination with 5-fluorouracil (5-FU), calcium folinate, and bevacizumab for the treatment of advanced solid tumors. Publicly available data shows that AZD9592 is aA bispecific antibody-drug conjugate (ADC) targeting EGFR and c-MET is currently in Phase 1 clinical trials internationally.。

Screenshot source: CDE official website

According to publicly available information from AstraZeneca, AZD9592 isThe company's first bispecific ADC product to enter clinical trials. This product was developed utilizing AstraZeneca's internally proprietary ADC technology, with TOP1i as the payload, targetingEpidermal Growth Factor Receptor (EGFR) and Mesenchymal-Epithelial Transition Tyrosine Kinase Receptor (c-MET）。It can target EGFR and c-Met proteins on the surface of cancer cells and directly deliver cytotoxic drugs to cancer cells. This targeted approach aims to minimize damage to healthy cells and reduce side effects.

Preclinical data show that AZD9592 has demonstrated favorable efficacy and safety in tumors expressing EGFR and c-MET, including but not limited to adenocarcinoma and squamous non-small cell lung cancer, as well as head and neck squamous cell carcinoma (HNSCC）. In addition, AstraZeneca alsoProposed Development of AZD9592To address the resistance issue of its third-generation EGFR tyrosine kinase inhibitor, Osimertinib。

According toClinicalTrialsOfficial website, AstraZeneca is conductingA Phase 1 First-in-Human Clinical Study of AZD9592 as Monotherapy or in Combination with Other Anticancer Drugs for the Treatment of Advanced Solid Tumors. This study will evaluate the safety, dosage, and preliminary efficacy of AZD9592 as monotherapy in patients with HNSCC and non-small cell lung cancer, as well as AZD9592 in combination with Osimertinib in patients with EGFR-mutated small cell lung cancer.

In China,A Phase 1 Clinical Study of AZD9592 for Advanced Solid Tumors Is Also Underway.This timeAZD9592 Approved for Two More Clinical Trials in China, Marking New Progress in the Clinical Research of the Product.

EGFR and c-METExpressed in a variety of solid tumors and acts as a driver gene in certain types of solid tumors. Public data shows that targetingEGFR andc-METBispecific antibody productsInEGFRThe clinical benefits in patients with mutant non-small cell lung cancer have been confirmed, but ADCs targeting these receptors are still in the development stage.In addition to AstraZeneca's AZD9592, several other ADC products have entered the clinical stage, such as those co-developed by Primus Bio and Hansoh Pharma.PM1080/HS-20117, which is currently in Phase 1 clinical research; the injectable drug developed by Provention BioPRO1286Already approved for clinical use in China this September.

[2]EGRET: A first-in-human study of the novel antibody-drug conjugate (ADC) AZD9592 as monotherapy or combined with other anticancer agents in patients (pts) with advanced solid tumors.. Retrieved May 31，2023 From https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.TPS3156#:~:text=AZD9592%20is%20an%20ADC%20with%20a%20bispecific%20Ab%20targeting%20EGFR