Based on DESTINY-Gastric02 which showed
Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by
In DESTINY-Gastric02, conducted in patients from
In DESTINY-Gastric01, conducted in patients from
In both trials, the safety profiles observed in patients treated with Enhertu were consistent with those seen in other trials of Enhertu with no new safety signals identified.
Enhertu is approved in the US and several other countries for locally advanced or metastatic HER2-positive gastric cancer.
Notes
HER2-positive gastric cancer
Gastric (stomach) cancer is the fifth most common cancer worldwide and the fourth highest leading cause of cancer mortality, with a five-year global survival rate of 5% to 10% for advanced or metastatic disease.3-5 Approximately one million new patients were diagnosed with gastric cancer in 2020, with 768,000 deaths reported globally.6 In Europe, approximately 136,000 cases of gastric cancer are diagnosed annually, and
Approximately one in five gastric cancers are HER2-positive.8,9 HER2 is a tyrosine kinase receptor growth promoting protein expressed on the surface of many types of tumours including breast, gastric, lung and colorectal cancers.8 HER2 overexpression may be associated with a specific HER2 gene alteration known as HER2 amplification.9
Recommended first-line treatment for HER2-positive advanced or metastatic gastric cancer is combination chemotherapy plus trastuzumab, an anti-HER2 medicine, which has been shown to improve survival outcomes when added to chemotherapy.10 For patients with metastatic gastric cancer that progresses following initial treatment with a trastuzumab-based regimen, treatment options are limited, and in many regions in the world there are no additional HER2 directed medicines available.2,11,12
DESTINY-Gastric02
DESTINY-Gastric02 is an open-label, single-arm Phase II trial in Western patients evaluating the efficacy and safety of Enhertu (6.4mg/kg) in patients with HER2-positive metastatic and/or unresectable gastric or GEJ adenocarcinoma with disease progression on or after a trastuzumab-containing regimen.
The primary endpoint of DESTINY-Gastric02 is confirmed ORR based on ICR. Secondary endpoints include progression-free survival (PFS), OS, DoR and safety.
DESTINY-Gastric02 enrolled 79 patients at multiple sites in
DESTINY-Gastric01
DESTINY-Gastric01 is a randomised, open-label Phase II trial evaluating the efficacy and safety of Enhertu (6.4mg/kg) in patients from
The primary endpoint of DESTINY-Gastric01 is ORR. Secondary endpoints include OS, PFS, DoR, disease control rate and time to treatment failure, as well as pharmacokinetic and safety endpoints.
DESTINY-Gastric01 enrolled 187 patients at multiple sites in
Enhertu
Enhertu is a HER2-directed ADC. Designed using
Enhertu (5.4mg/kg) is approved in more than 35 countries for the treatment of adult patients with unresectable or metastatic HER2-positive 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 several countries for the treatment of adult patients with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial.
Enhertu (5.4mg/kg) is approved in
Enhertu (5.4mg/kg) is approved under accelerated approval in the US for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer whose tumours have activating HER2 (ERBB2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy, based on the results of the DESTINY-Lung02 trial. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Enhertu (6.4mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2-positive gastric or GEJ who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.
Enhertu development programme
A comprehensive development programme is underway globally, evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.
Regulatory applications for Enhertu in breast and gastric cancer are currently under review in several other countries based on the DESTINY-Breast01, DESTINY-Breast03, DESTINY-Breast04, DESTINY-Gastric01 and DESTINY-Gastric02 trials, respectively.
Within this programme, the Company is committed to improving outcomes in gastric, liver, biliary tract, oesophageal, pancreatic and colorectal cancers.
Enhertu, a HER2-directed antibody drug conjugate, is approved in the US and several other countries for HER2-positive advanced gastric cancer and is being assessed in colorectal cancer. Enhertu is jointly developed and commercialised by
Imfinzi (durvalumab) is approved in the US and several other countries in combination with chemotherapy (gemcitabine plus cisplatin) for advanced biliary tract cancer and in the US in combination with Imjudo (tremelimumab) in unresectable hepatocellular carcinoma. Imfinzi is being assessed in combinations, including with Imjudo, in liver, oesophageal and gastric cancers in an extensive development programme spanning early to late-stage disease across settings.
Lynparza (olaparib), a first-in-class PARP inhibitor, is approved in the US and several other countries for the treatment of BRCA-mutated metastatic pancreatic cancer. Lynparza is developed and commercialised in collaboration with MSD (
The Company's focus is on some of the most challenging cancers. It is through persistent innovation that
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References
1. Updated analysis of DESTINY-Gastric02. Available at: https://oncologypro.esmo.org/meeting-resources/esmo-congress/updated-analysis-of-destiny-gastric02-a-phase-ii-single-arm-trial-of-trastuzumab-deruxtecan-t-dxd-in-western-patients-pts-with-her2-positive. Accessed
2. Shitara K, et al. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med 2020; 382:2419-2430.
3. Casamayor M, et al. Targeted literature review of the global burden of gastric cancer. Ecancermedicalscience. 2018; 12:883;12:883.
4. SEER Cancer Stat Facts: Stomach Cancer. Available at: https://seer.cancer.gov/statfacts/html/stomach.html. Accessed
5. Sung. H et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021; 10.3322/caac.21660.
6. WHO.
7.
8. Iqbal N, et al. Human Epidermal Growth Factor Receptor 2 (HER2) in Cancers: Overexpression and Therapeutic Implications. Mol Biol Int. 2014; 2014:852748.
9. Abrahao-Machado LF, et al. HER2 testing in gastric cancer: An update. World J Gastroenterol. 2016; 22(19):4619-4625.
10. Orditura M, et al. "Treatment of gastric cancer."
11. Thuss-Patience PC, et al. Trastuzumab emtansine versus taxane use for previously treated HER2-positive locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma (GATSBY): an international randomised, open-label, adaptive, phase 2/3 study. Lancet Oncol. 2017; 18(5):640-653.
12. Satoh T, et al. Lapatinib Plus Paclitaxel Versus Paclitaxel Alone in the Second-Line Treatment of HER2-Amplified Advanced Gastric Cancer in Asian Populations: TyTAN-A Randomized, Phase III Study. J Clin Oncol.2014; 32(19):2039-2049.
13. WHO. World Cancer Fact Sheet. Available at: https://gco.iarc.fr/today/data/factsheets/populations/900-world-fact-sheets.pdf. Accessed
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