ENHERTU® Recommended for Approval in the EU by CHMP for Patients with Previously Treated HER2 Positive Advanced Gastric Cancer
Based on DESTINY-Gastric02, which showed
Daiichi Sankyoand AstraZeneca’s ENHERTU demonstrated clinically meaningful efficacy and DESTINY-Gastric01, which showed improved overall survival compared to chemotherapy
ENHERTU is a specifically engineered HER2 directed antibody drug conjugate (ADC) being jointly developed and commercialized by
In DESTINY-Gastric02, conducted in patients from
In DESTINY-Gastric01, conducted in patients from
The recommendation will now be reviewed by the
“ENHERTU is the first HER2 directed medicine to demonstrate a significant improvement in overall survival compared to chemotherapy in patients with gastric cancer following initial treatment with a HER2 directed medicine in the advanced or metastatic setting,” said
“Gastric cancer is usually diagnosed in the advanced stage in many European countries and patients face high mortality rates,” said
In DESTINY-Gastric02, the safety profile observed with patients treated with ENHERTU was consistent with that seen in other trials of ENHERTU with no new safety signals identified. Grade 3 or higher treatment-emergent adverse events (TEAEs) occurred in 55.7% of patients receiving ENHERTU 6.4 mg/kg. The most common grade 3 or higher treatment-related TEAEs occurring in ≥10% of patients receiving ENHERTU was anemia (13.9%). There were eight cases (10.1%) of treatment-related interstitial lung disease (ILD) or pneumonitis as determined by an independent adjudication committee. The majority (six) were low grade (grade 1 or 2), with two grade 5 ILD or pneumonitis events reported.
In DESTINY-Gastric01, the safety profile observed in patients treated with ENHERTU was consistent with that seen in other trials of ENHERTU with no new safety signals identified. Grade 3 or higher TEAEs occurred in 85.6% of patients receiving ENHERTU 6.4 mg/kg. The most common grade 3 or higher treatment-related TEAEs occurring in ≥20% of patients receiving ENHERTU were decreased neutrophil count (51.2%), anemia (38.4%) and decreased white blood cell count (20.8%). There were 16 cases (12.8%) of treatment-related ILD or pneumonitis as determined by an independent adjudication committee. The majority (13) were low grade (grade 1 or 2), with two grade 3 events and one grade 4 event reported. No grade 5 ILD or pneumonitis events occurred.
ENHERTU is not currently approved in the EU for the treatment of advanced gastric cancer and is subject to additional monitoring.
DESTINY-Gastric02 is an open-label, single-arm phase 2 trial in Western patients evaluating the efficacy and safety of ENHERTU (6.4 mg/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 is a randomized, open-label phase 2 trial evaluating the efficacy and safety of ENHERTU (6.4 mg/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
About 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.1,2,3 Approximately one million new patients were diagnosed with gastric cancer in 2020, with 768,000 deaths reported globally.4 In
Approximately one in five gastric cancers are HER2 positive.7,8 HER2 is a tyrosine kinase receptor growth promoting protein expressed on the surface of many types of tumors including breast, gastric, lung and colorectal cancers.7 HER2 overexpression may be associated with a specific HER2 gene alteration known as HER2 amplification.8
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.9,10 For patients with metastatic gastric cancer that progresses following initial treatment with a trastuzumab-based regimen, treatment options are limited, and in many regions of the world there are no additional HER2 directed medicines available.1,11,12
ENHERTU (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the
ENHERTU (5.4 mg/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 also 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 (5.4 mg/kg) is approved in
ENHERTU (5.4 mg/kg) is approved under accelerated approval in the
ENHERTU (6.4 mg/kg) is approved in several countries for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.
About the ENHERTU Clinical Development Program
A comprehensive global development program is underway 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 countries based on the DESTINY-Breast01, DESTINY-Breast03, DESTINY-Breast04, DESTINY-Gastric01 and DESTINY-Gastric02 trials, respectively.
1 Casamayor M, et al. Ecancermedicalscience. 2018;12:883.
2 SEER Cancer Stat Facts: Stomach Cancer 2012-2018. Accessed
3 Sung H, et al. Ca Cancer J Clin. 2021;71:209–249.
4 WHO. Stomach Cancer Fact Sheet. Accessed
5 WHO. Cancer Today Europe Mortality. Accessed
7 Iqbal N, et al. Mol Biol Int. 2014;2014:852748.
8 Abrahao-Machado LF, et al. World J Gastroenterol. 2016;22(19):4619-4625.
9 Oditura M, et al. World J Gastroenterol. 2014 Feb 21;20(7):1635-49.
10 Lordick F, et al. Annals of Oncology. 2022; 33(10):1012.
11 Thuss-Patience PC, et al. Lancet Oncol. 2017;18(5):640-653.
12 Satoh T, et al. J Clin Oncol. 2014;32(19):2039‐2049.
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