• 15 Oct 2024
• Admin
• News Article

AstraZeneca & Daiichi Sankyo’s Enhertu Gets Conditional Approval from China NMPA

China NMPA grants conditional approval to AstraZeneca & Daiichi Sankyo’s Enhertu as first HER2-directed therapy for patients with HER2-mutant metastatic NSCLC

Overview

AstraZeneca and Daiichi Sankyo’s Enhertu (trastuzumab deruxtecan) has received conditional approval in China as a monotherapy for the treatment of adult patients with unresectable, locally advanced or metastatic non-small cell lung cancer (NSCLC) whose tumours have activating HER2 (ERBB2) mutations and who have received a prior systemic therapy.

Behind the Approval

• The conditional approval by the National Medical Products Administration (NMPA) was based on the positive results of the DESTINY-Lung02 and DESTINY-Lung05 phase II trials. 
• Full approval for this indication will depend on the clinical benefit of a confirmatory trial.

Lung Cancer in China

Each year in China, more than one million people are diagnosed with lung cancer, accounting for more than 40% of the world’s lung cancer patients – the majority are diagnosed with advanced disease. Approximately 2% to 4% of patients with NSCLC have tumours with activating HER2 mutations.

From Principal Investigator of DESTINY-Lung05

Ying Cheng, MD, PhD, director of Jilin Lung Cancer Centre, China, and principal investigator of DESTINY-Lung05, said: “While there have been many advancements in the treatment of non-small cell lung cancer in China in recent years, patients with HER2-mutant disease have had few treatment options and none directed towards this specific type of lung cancer. This approval of Enhertu offers an important new targeted treatment for patients with this aggressive form of disease.”

Statement from the AstraZeneca

Dave Fredrickson, executive vice president, oncology business unit, AstraZeneca, said: “This approval of Enhertu represents the first HER2-directed therapy approved in China for the treatment of HER2-mutant metastatic non-small cell lung cancer, marking an important step forward in how the disease can be treated. It also reinforces the importance of testing for predictive biomarkers in lung cancer at the time of diagnosis, including HER2 mutations, to ensure patients can receive the most appropriate treatment for their specific disease.”

Statement from the Daiichi Sankyo

• Kiminori Nagao, head of the Asia, South & Central America Business Unit, Daiichi Sankyo, said: “Since our initial approval of Enhertu for patients with HER2-positive metastatic breast cancer in China last year, we have remained committed to bringing this innovative antibody drug conjugate to more patients in China, especially those that have previously not been eligible for treatment with a HER2-directed therapy.”
• Today’s milestone marks the fourth approval of Enhertu in China and follows the recent approval for HER2-positive metastatic gastric cancer, reinforcing its benefit across multiple HER2-targetable tumours.”

About DESTINY-Lung02 Trial

• In DESTINY-Lung02, which included patients from Japan, Korea and Taiwan (China), patients with previously treated HER2-mutant metastatic NSCLC treated with Enhertu (5.4mg/kg) showed a confirmed objective response rate (ORR) of 49.0% (95% confidence interval [CI] 39.0-59.1), as assessed by blinded independent central review (BICR). 
• Median duration of response (DoR) was 16.8 months (95% CI 6.4-non-evaluable [NE]). 
• Median progression-free survival (PFS) was 9.9 months (95% CI 7.4-NE) and median overall survival (OS) was 19.5 months (95% CI 13.6-NE).
• In DESTINY-Lung05, Enhertu (5.4mg/kg) demonstrated a consistent clinically meaningful response in patients in China with previously treated HER2-mutant metastatic NSCLC. 
• Treatment with Enhertu resulted in a confirmed ORR of 58.3% (95% CI 46.1-69.8), as assessed by independent central review (ICR).

The safety profile of Enhertu in DESTINY-Lung02 and DESTINY-Lung05 were similar and generally consistent with previous clinical trials of Enhertu in lung cancer with no new safety concerns identified.

About Enhertu

Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

Previous Approvals

Enhertu is already approved for the treatment of previously treated unresectable or metastatic HER2-mutant NSCLC in more than 45 countries, including the US, Japan and across the EU.

About Lung Cancer

• Lung cancer is the most common form of cancer globally in both men and women.
• Each year there are approximately 2.5 million people diagnosed with lung cancer globally, with 80-85% diagnosed with NSCLC.
• Prognosis is poor for patients with metastatic NSCLC as only approximately 9% will live beyond five years after diagnosis.

In China

In China, lung cancer is the most commonly diagnosed cancer with more than one million cases diagnosed in 2022. It is also the leading cause of cancer-related deaths in China, with more than 733,000 deaths reported in 2022.

About HER2 Protein

• HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of multiple tumour types. 
• Certain HER2 (ERBB2) gene alterations (called HER2 mutations) have been identified in patients with non-squamous NSCLC as a distinct molecular target, and occur in approximately 2% to 4% of patients with this type of lung cancer. 
• While HER2 gene mutations can occur in a range of patients, they are more commonly found in patients with NSCLC who are younger, female and have never smoked. 
• HER2 gene mutations have been independently associated with cancer cell growth and poor prognosis, with an increased incidence of brain metastases. 
• Next-generation sequencing has been utilised in the identification of HER2 (ERBB2) mutations.

About DESTINY-Lung02

• DESTINY-Lung02 is a global, randomised phase II trial evaluating the safety and efficacy of Enhertu in patients with HER2-mutant unresectable and/or metastatic NSCLC with disease recurrence or progression during or after at least one regimen of prior anticancer therapy that must have contained a platinum-based chemotherapy. 
• Patients were randomised 2:1 to receive Enhertu 5.4mg/kg (n=102) or Enhertu 6.4mg/kg (n=50).
• The primary endpoint of the trial is confirmed ORR as assessed by BICR. 
• Secondary endpoints include disease control rate (DCR), DoR and PFS assessed by investigator and BICR, OS and safety.
• DESTINY-Lung02 enrolled 152 patients at multiple sites, including Asia, Europe, Oceania and North America.

About DESTINY-Lung05 Study

• DESTINY-Lung05 is an open-label, single-arm phase II trial evaluating the safety and efficacy of Enhertu (5.4mg/kg) in patients with HER2-mutant metastatic NSCLC with disease progression on or after at least one prior anticancer therapy.
• The primary endpoint of the trial is confirmed ORR as assessed by ICR. Secondary endpoints include investigator-assessed confirmed ORR, as well as ICR and investigator-assessed DoR, DCR, PFS and safety.
• DESTINY-Lung05 enrolled 72 patients at multiple sites in China.

About the Enhertu

• Enhertu is a HER2-directed ADC. Designed using Daiichi Sankyo’s proprietary DXd ADC Technology, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. 
• Enhertu consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Enhertu: Approvals

• Enhertu (5.4mg/kg) is approved in more than 65 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (immunohistochemistry [IHC 3+ or in-situ hybridisation [ISH]+) breast cancer who have received a (or one or more)  prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.
• Enhertu (5.4mg/kg) is approved in more than 65 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.
• Enhertu (5.4mg/kg) is approved in more than 45 countries worldwide for the treatment of adult patients with unresectable or metastatic NSCLC whose tumours have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
• Enhertu (6.4mg/kg) is approved in more than 45 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric06 trials. Continued approval in China for this indication will depend on whether a randomised controlled confirmatory clinical trial can demonstrate clinical benefit in this population.
• Enhertu (5.4mg/kg) is approved in the US for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01 and DESTINY-CRC02 trials. Continued approval for this indication in the US may be contingent upon verification and description of clinical benefit in a confirmatory trial.

About Global Clinical Development Programme

A comprehensive global clinical development programme is underway evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers. Trials in combination with other anti-cancer treatments, such as immunotherapy, also are underway.

About the Collaboration

• AstraZeneca and Daiichi Sankyo entered into a global collaboration to jointly develop and commercialise Enhertu in March 2019 and datopotamab deruxtecan in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. 
• Daiichi Sankyo is responsible for the manufacturing and supply of Enhertu and datopotamab deruxtecan.