Approval based on DESTINY-Gastric06 results which showed Enhertu demonstrated clinically meaningful efficacy in this setting
Third approval in China for AstraZeneca and Daiichi Sankyo's Enhertu in less than two years

AstraZeneca and Daiichi Sankyo's Enhertu (trastuzumab deruxtecan) has received conditional approval in China as a monotherapy for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received two or more prior treatment regimens.

The conditional approval by the National Medical Products Administration (NMPA) was based on the positive results of the DESTINY-Gastric06 Phase II trial. Full approval for this indication will depend on whether a randomised controlled confirmatory clinical trial can demonstrate clinical benefit in this population.

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.

In the DESTINY-Gastric06 trial, Enhertu demonstrated clinically meaningful efficacy in patients in China with locally advanced or metastatic HER2-positive gastric or GEJ adenocarcinoma previously treated with two or more prior regimens including a fluoropyrimidine agent and a platinum agent.

More than one third of the global cases of gastric cancer occur in China, with about 65% of patients presenting with advanced disease at the time of diagnosis.1-3 Approximately 359,000 new cases of gastric cancer and 260,000 deaths were reported in China in 2022.1 Roughly one in five gastric cancers globally are HER2-positive.4,5

Lin Shen, MD, Director of the Department of Gastrointestinal Oncology, Peking University Cancer Hospital, China, said: "HER2-positive metastatic gastric cancer can be particularly aggressive and difficult to treat. Patients often face poor outcomes following disease progression on first-line treatment and subsequent chemotherapy. With the approval of Enhertu, patients in China with HER2-positive metastatic gastric cancer will now have an important anti-HER2 treatment option that has demonstrated clinically meaningful efficacy following progression on previous therapies."

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: "China accounts for more than a third of patients with gastric cancer globally and most patients are diagnosed with advanced disease. This approval of Enhertu brings a much-needed, new targeted treatment option to patients with HER2-positive metastatic gastric cancer in China and underscores our commitment to bringing this innovative medicine to more patients across the globe living with HER2-expressing cancers."

Kiminori Nagao, Head of the Asia, South & Central America Business Unit, Daiichi Sankyo, said: "This milestone marks the third approval in China for Enhertu in less than two years, following approvals for HER2-positive metastatic breast cancer and HER2-low metastatic breast cancer. Our DESTINY clinical trial programme continues to reinforce Enhertu as a practice-changing treatment option for patients with HER2-expressing cancers and this latest approval in China further illustrates the global impact of this innovative antibody drug conjugate."

In DESTINY-Gastric06, treatment with Enhertu (6.4mg/kg) resulted in a confirmed objective response rate (ORR) of 28.8% as assessed by independent central review. Median progression-free survival (PFS) was 5.7 months.

The safety profile of Enhertu in DESTINY-Gastric06 was consistent with previous clinical trials of Enhertu in gastric cancer with no new safety concerns identified.

The approval was also supported by results from the DESTINY-Gastric01 Phase II trial which included patients from Japan and South Korea. In the trial, patients with HER2-positive metastatic gastric cancer treated with Enhertu showed a statistically significant improvement in confirmed ORR (40.5% with Enhertu versus 11.3% with chemotherapy; p<0.0001) and median overall survival (OS) (12.5 months with Enhertu versus 8.4 months with chemotherapy; hazard ratio [HR] 0.59; 95% confidence interval [CI] 0.39-0.88; p=0.0097).

Enhertu is already approved for advanced or metastatic gastric cancer in more than 45 countries, including the US, Japan and across the EU.

Notes

HER2-positive gastric cancer
Gastric (stomach) cancer is the fifth most common cancer worldwide and the fifth leading cause of cancer-related death, with a five-year global survival rate of 5% to 10% for advanced or metastatic disease.2,6 Approximately one million new patients were diagnosed with gastric cancer in 2022, with more than 660,000 deaths reported globally.2

Incidence rates for gastric cancer are markedly higher in eastern Asia, particularly in China where more than one third of all global cases occur.1,2 Gastric cancer is the fifth most common cancer in China with about 359,000 new cases diagnosed in 2022.1 Additionally, it is the third leading cause of cancer-related death in China with approximately 260,000 deaths reported in 2022.1 Approximately 65% of patients in China present with advanced disease at the time of diagnosis.3

Approximately one in five gastric cancers globally are HER2-positive.4,5 HER2 is a tyrosine kinase receptor growth promoting protein expressed on the surface of many types of tumours, including gastric cancer.5

Recommended first-line treatment in China for HER2-positive advanced or metastatic gastric cancer is combination chemotherapy and trastuzumab, an anti-HER2 medicine, with or without pembrolizumab.7 For patients that progress following initial treatment with a trastuzumab-based regimen, subsequent anti-HER2 treatment options are limited.7

DESTINY-Gastric06
DESTINY-Gastric06 is an open-label, single-arm Phase II trial in China evaluating the safety and efficacy of Enhertu (6.4mg/kg) in patients with HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma previously treated with two or more prior regimens including a fluoropyrimidine agent and a platinum agent.

The primary endpoint is confirmed ORR by independent central review. Secondary endpoints include investigator-assessed ORR, PFS, duration of response (DoR), disease control rate (DCR), OS and safety.

DESTINY-Gastric06 enrolled 95 patients at multiple sites in China. For more information about the trial, visit clinicaltrials.gov.

DESTINY-Gastric01
DESTINY-Gastric01 is a Phase II, open-label, multi-centre, randomised controlled trial testing the safety and efficacy of Enhertu (6.4mg/kg) versus investigator's choice of chemotherapy in a primary cohort of patients from Japan and South Korea with HER2-positive locally advanced or metastatic gastric or GEJ adenocarcinoma who have progressed on at least two or more prior regimens including trastuzumab plus a fluoropyrimidine- and platinum-based chemotherapy combination.

Patients (n=188) were randomised 2:1 to receive Enhertu or physician's choice of chemotherapy (paclitaxel or irinotecan monotherapy).

The primary endpoint is ORR assessed by independent central review. OS is a key secondary endpoint. Additional secondary endpoints include PFS, DoR, disease control rate and safety.

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 (5.4mg/kg) is approved in more than 65 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or in-situ hybridization [ISH]+) breast cancer who have received a 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 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 35 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 trial. Continued approval in 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 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. Full approval in China for this indication will depend on whether the 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 in the US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu 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.

Daiichi Sankyo 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.

AstraZeneca in oncology
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