Enhertu Gains Conditional Approval in China for Advanced HER2-Positive Gastric Cancer Treatment

Enhertu Gains Conditional Approval in China for Advanced HER2-Positive Gastric Cancer Treatment

(IN BRIEF) AstraZeneca and Daiichi Sankyo’s Enhertu has received conditional approval in China for treating locally advanced or metastatic HER2-positive gastric cancer, following promising results from the DESTINY-Gastric06 trial. This marks the third approval for Enhertu in China in less than two years, underscoring its growing significance in treating HER2-expressing cancers. Full approval will require further confirmation of its clinical benefits.

(PRESS RELEASE) CAMBRIDGE, 13-Aug-2024 — /EuropaWire/ — AstraZeneca and Daiichi Sankyo’s innovative cancer treatment, Enhertu (trastuzumab deruxtecan), has received conditional approval in China for use as a monotherapy in adult patients with locally advanced or metastatic HER2-positive gastric or gastroesophageal junction (GEJ) adenocarcinoma. This approval is specifically for patients who have already undergone two or more prior treatment regimens.

The approval by China’s National Medical Products Administration (NMPA) is based on promising results from the DESTINY-Gastric06 Phase II trial, which demonstrated significant efficacy of Enhertu in this patient group. A full approval will depend on further confirmation of these benefits through a randomized controlled clinical trial.

Enhertu, an advanced HER2-directed antibody drug conjugate (ADC), was developed by Daiichi Sankyo and is being co-developed and commercialized in partnership with AstraZeneca. This approval marks the third time in less than two years that Enhertu has been approved in China, highlighting the drug’s growing impact in the treatment of HER2-positive cancers.

The DESTINY-Gastric06 trial, conducted in China, revealed that Enhertu achieved a confirmed objective response rate (ORR) of 28.8% and a median progression-free survival (PFS) of 5.7 months in patients with advanced HER2-positive gastric or GEJ adenocarcinoma. The safety profile of Enhertu in this trial was consistent with previous studies, with no new safety concerns identified.

Dr. Lin Shen, Director of the Department of Gastrointestinal Oncology at Peking University Cancer Hospital, emphasized the significance of this approval, noting that HER2-positive metastatic gastric cancer is particularly aggressive and difficult to treat, with limited options available after the failure of initial therapies. Enhertu offers a new, important treatment option for these patients.

Dave Fredrickson, Executive Vice President of the Oncology Business Unit at AstraZeneca, noted that China accounts for more than a third of global gastric cancer cases, making this approval a critical milestone in providing new treatment options for patients in the region. Kiminori Nagao, Head of the Asia, South & Central America Business Unit at Daiichi Sankyo, added that this approval further reinforces Enhertu’s role as a transformative treatment option for patients with HER2-expressing cancers.

Enhertu is already approved for the treatment of advanced or metastatic gastric cancer in over 45 countries, including the US, Japan, and across the EU. The drug’s ongoing development is supported by a comprehensive global clinical program, exploring its efficacy across multiple HER2-targetable cancers.

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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The Company’s focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

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References

1. WHO. International Agency of Cancer Research. Cancer Today. China. 2022. Available at: https://gco.iarc.who.int/media/globocan/factsheets/populations/160-china-fact-sheet.pdf. Accessed August 2024.

2. WHO. International Agency of Cancer Research. Cancer Today. Stomach. 2022. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/7-stomach-fact-sheet.pdf. Accessed August 2024.

3. Zeng H, et al. Disparities in stage at diagnosis for five common cancers in China: a multicentre, hospital-based, observational study. Lancet Public Health. 2021; Dec;6(12):e877-e887.

4. Iqbal N, et al. Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications. Mol Biol Int. 2014; 852748.

5. Abrahao-Machado LF, et al. HER2 testing in gastric cancer: An update. World J Gastroenterol. 2016;22(19):4619-4625.

6. Casamayor M, et al. Targeted literature review of the global burden of gastric cancer.  Ecancermedicalscience. 2018;12:883.

7. Wang F, et al. The Chinese Society of Clinical Oncology (CSCO): Clinical guidelines for the diagnosis and treatment of gastric cancer, 2023. Cancer Commun (Lond). 2024 Jan;44(1):127-172.

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