Trastuzumab Deruxtecan (Enhertu) for HER2-Positive Gastric Cancer Submitted for Priority Review in China

Nov 07, 2023 14:04 CST Updated 14:05

AstraZeneca

Biopharmaceutical Manufacturer

Daiichi-Sankyo

Pharmaceutical R&D Developer

▎WuXi AppTec Content Team Report

November 6,China's National Medical Products Administration (NMPA) Center for Drug Evaluation (CDE) announced that a new indication for Daiichi Sankyo's trastuzumab deruxtecan injection has been proposed for priority review.Monotherapy is indicated for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received two or more prior treatment regimens.. Public information shows that Trastuzumab Deruxtecan (Enhertu) is jointly developed by AstraZeneca and Daiichi Sankyo.A HER2-targeted antibody-drug conjugate (ADC) that was previously approved in China for the treatment of HER2-positive and HER2-low adult breast cancer patients.。

Screenshot source:CDE Official Website

Gastric cancer is a common cancer globally and one of the leading causes of cancer-related deaths. Adenocarcinoma is the predominant histological subtype of gastric cancer, accounting for over 90% of reported cases worldwide. According to statistics, most Chinese patients with gastric cancer are diagnosed at an advanced stage, leaving limited treatment options. Approximately one in five gastric cancers is HER2-positive. HER2 is a tyrosine kinase receptor expressed in many types of tumors, including breast cancer, gastric cancer, and colorectal cancer.

Trastuzumab Deruxtecan byHumanized monoclonal antibody targeting HER2Through a cleavable tetrapeptide linker withTopoisomerase 1 InhibitorPayload connection composition. The drug'sMechanism of ActionFirst, the antibody portion of the drug targets and attaches to HER2 on cancer cells; then, trastuzumab deruxtecan enters the cancer cells and releases the chemotherapy agent, where the chemotherapy component of the ADC kills the cancer cells as well as nearby cells.

In February 2023, Trastuzumab Deruxtecan in ChinaApprovedTreatment of unresectable or metastatic disease previously treated with one or more anti-HER2 drugsHER2-Positive Adult Breast CancerPatient; Same YearIn July, the new indication for this productRe-approved, Monotherapy is applicable toPreviously received at least one systemic treatment at the metastatic disease stage, or relapsed within 6 months during or after adjuvant chemotherapy, unresectable or metastaticHER2-Low Expressing Adult Breast CancerPatient.According to the CDE announcement, this time Trastuzumab Deruxtecan is proposed to be included in the priority review, targeting the indication ofHER2-Positive Adult Gastric or Gastroesophageal Junction Adenocarcinoma。

Previously, Trastuzumab Deruxtecan had beenA treatmentPatients with HER2-positive locally advanced or metastatic gastric cancer and gastroesophageal junction adenocarcinomaRandomized Phase 2DESTINY-Gastric01Positive results were achieved in the trial. The data shows,Compared with patients receiving chemotherapy,Patients receiving treatment with this productObjective response rate (51.3% vs 14.3%) and overall survival (median OS: 12.5 months vs 8.4 months) showed significant improvement.. In a pre-specified interim analysis, patients receiving trastuzumab deruxtecan were compared with those receiving chemotherapy,The risk of death was reduced by 41%.. Based on the research results, the product hasObtained FDA ApprovalExpanded indication for the treatment of patients with HER2-positive locally advanced or metastatic gastric cancer and gastroesophageal junction adenocarcinoma.

In another code-named study targeting Western patients with gastric cancer,DESTINY-Gastric02In the Phase 2 clinical trial, Trastuzumab Deruxtecan also demonstrated positive efficacy results in treating HER2-positive metastatic or unresectable gastric cancer or gastroesophageal junction adenocarcinoma. The main analysis of the trial showed that Trastuzumab DeruxtecanAchieved a 38% overall response rate (ORR), including a 3.8% complete response (CR) and a 34.2% partial response (PR).. At a median follow-up time of 5.7 months, the median duration of response was 8.1 months, and the progression-free survival was 5.5 months.

References:

[1] Center for Drug Evaluation (CDE) of the National Medical Products Administration (NMPA) of China. Retrieved Nov 6, 2023, from https://www.cde.org.cn/main/xxgk/listpage/2f78f372d351c6851af7431c7710a731

[2]Enhertu label. Retrieved Jan 15, 2021, from https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761139s011lbl.pdf

[3] The Phase II clinical trial DESTINY-Gastric02 of Enhertu highlights its clinical significance and durable response in HER2-positive advanced gastric cancer patients. Retrieved Sep 20, 2021, from https://mp.weixin.qq.com/s/0L_gMLFmSmuHvGsjGsSmhg

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