TOKYO, Japan & MUNICH, Germany & BASKING RIDGE, NJ, USA I July 8, 2021 I Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and AstraZeneca today announced that the first patient was dosed in DESTINY-Gastric04, a global phase 3 trial evaluating the safety and efficacy of ENHERTU® (trastuzumab deruxtecan) compared to ramucirumab/paclitaxel combination therapy in patients with HER2 positive metastatic and/or unresectable gastric or gastroesophageal junction (GEJ) adenocarcinoma with disease progression on or after a trastuzumab-containing regimen.
Gastric cancer is associated with a poor prognosis, particularly in the advanced stages of the disease, with only 5% to 10% of patients surviving 5 years.1 One in five gastric cancers are considered HER2 positive,2,3 however loss of HER2 expression has been observed in 29% to 69% of patients with gastric cancer following treatment with trastuzumab, suggesting a decrease in HER2 expression can result in progression on trastuzumab and may be associated with poor outcomes.4,5,6,7,8 After progression on first-line HER2 targeted systemic treatment, second-line treatment options are limited, driving a need for new HER2 targeted therapies for these patients.1,7,8
“In the DESTINY-Gastric04 phase 3 trial, we are evaluating whether ENHERTU will improve survival as compared to another commonly used combination therapy regimen in the second-line HER2 positive metastatic gastric cancer setting,” said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. “Results from our earlier research have led to approvals of ENHERTU in two regions for patients with HER2 positive metastatic gastric cancer and we are excited to continue our research in this patient population to further support our efforts to bring a new treatment option to more patients around the world.”
About DESTINY-Gastric04
DESTINY-Gastric04 is a global, randomized, open-label, head-to-head phase 3 trial evaluating the safety and efficacy of ENHERTU (6.4mg/kg) compared to ramucirumab/paclitaxel combination therapy in patients with HER2 positive metastatic and/or unresectable gastric or GEJ adenocarcinoma with disease progression on or after a trastuzumab-containing regimen.
Patients will be randomized to receive either ENHERTU or ramucirumab/paclitaxel. The primary endpoint of DESTINY-Gastric04 is overall survival. Secondary endpoints include investigator assessed progression-free survival, objective response rate, duration of response, disease control rate, safety, pharmacokinetics and immunogenicity.
DESTINY-Gastric04 will enroll approximately 490 patients at multiple sites in Asia, Europe and South America. For more information about the trial, visit ClinicalTrials.gov.
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 survival rate of 5% to 10% for advanced or metastatic disease.1,9 There were approximately one million new cases of gastric cancer and 768,000 deaths reported worldwide in 2020.10 Incidence rates for gastric cancer are markedly higher in eastern Asia, where approximately half of all cases occur.1,10,11 Gastric cancer is typically diagnosed in the advanced stage but even when diagnosed in earlier stages of the disease the survival rate remains modest.4,12,13
Approximately one in five gastric cancers are considered HER2 positive.2,3 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.3 HER2 overexpression may be associated with a specific HER2 gene alteration known as HER2 amplification.3
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.11 However, loss of HER2 expression has been observed in 29% to 69% of patients with gastric cancer following treatment with trastuzumab, suggesting a decrease in HER2 expression can result in progression on trastuzumab and may be associated with poor outcomes in gastric cancer. 4,5,6,7,8 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.1,7,8
About ENHERTU
ENHERTU® (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the U.S. only) is a HER2 directed antibody drug conjugate (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 program in AstraZeneca’s ADC scientific platform. ENHERTU consists of a HER2 monoclonal antibody attached to a topoisomerase I inhibitor payload, an exatecan derivative, via a stable tetrapeptide-based cleavable linker.
ENHERTU (5.4 mg/kg) is approved in Canada, EU, Japan, UK and in the U.S., 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 in the metastatic setting based on the results from the DESTINY-Breast01 trial.
ENHERTU (6.4 mg/kg) is also approved in the U.S. and Japan for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01 trial.
ENHERTU is approved in the U.S. with Boxed WARNINGS for Interstitial Lung Disease and Embryo-Fetal Toxicity. For more information, please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.
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.
ENHERTU was recently highlighted in the Clinical Cancer Advances 2021 report as one of two significant advancements in the “ASCO Clinical Advance of the Year: Molecular Profiling Driving Progress in GI Cancers,” based on data from both the DESTINY-CRC01 and DESTINY-Gastric01 trials.
In May 2020, ENHERTU received Breakthrough Therapy Designation (BTD) in the U.S. for the treatment of patients with metastatic non-small cell lung cancer whose tumors have a HER2 mutation and with disease progression on or after platinum-based therapy.
About the Daiichi Sankyo and AstraZeneca Collaboration
Daiichi Sankyo and AstraZeneca entered into a global collaboration to jointly develop and commercialize ENHERTU in March 2019, and datopotamab deruxtecan (Dato-DXd) in July 2020, except in Japan where Daiichi Sankyo maintains exclusive rights for each ADC. Daiichi Sankyo is responsible for manufacturing and supply of ENHERTU and datopotamab deruxtecan.
U.S. Important Safety Information for ENHERTU
Indications
ENHERTU is a HER2-directed antibody and topoisomerase inhibitor conjugate indicated 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 in the metastatic setting.
This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. - Locally advanced or metastatic HER2-positive gastric or gastroesophageal junction adenocarcinoma who have received a prior trastuzumab-based regimen.
Please see accompanying full Prescribing Information, including Boxed WARNINGS, and Medication Guide.
About Daiichi Sankyo in Oncology
The oncology portfolio of Daiichi Sankyo is powered by our team of world-class scientists that push beyond traditional thinking to create transformative medicines for people with cancer. Anchored by our DXd antibody drug conjugate (ADC) technology, our research engines include biologics, medicinal chemistry, modality and other research laboratories in Japan, and Plexxikon Inc., our small molecule structure-guided R&D center in the U.S. We also work alongside leading academic and business collaborators to further advance the understanding of cancer as Daiichi Sankyo builds towards our ambitious goal of becoming a global leader in oncology by 2025.
About Daiichi Sankyo
Daiichi Sankyo is dedicated to creating new modalities and innovative medicines by leveraging our world-class science and technology for our purpose “to contribute to the enrichment of quality of life around the world.” In addition to our current portfolio of medicines for cancer and cardiovascular disease, Daiichi Sankyo is primarily focused on developing novel therapies for people with cancer as well as other diseases with high unmet medical needs. With more than 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 16,000 employees around the world draw upon a rich legacy of innovation to realize our 2030 Vision to become an “Innovative Global Healthcare Company Contributing to the Sustainable Development of Society.” For more information, please visit: www.daiichisankyo.com.
References:
1 Casamayor M, et al. Ecancermedicalscience. 2018;12:883.
2 Iqbal N, et al. Mol Biol Int. 2014;2014:852748.
3 Abrahao-Machado LF, et al. World J Gastroenterol. 2016;22(19):4619-4625.
4 Zhao D, et al. J Hematol Oncol. 2019;12(1):50.
5 Seo S, et al. Gastric Cancer. 2019;22(3):527-535.
6 Kijima T, et al. Anticancer Res. 2020;40(1):75-80.
7 Thuss-Patience PC, et al. Lancet Oncol. 2017;18(5):640-653.
8 Satoh T, et al. J Clin Oncol. 2014;32(19):2039‐2049.
9 Sung H, et al. CA: A Cancer Journal for Clinicians. 2021 May;71(3):209-249.
10 WHO. International Agency of Cancer Research. Cancer Today. Accessed May 2021.
11 Oditura M, et al. World J Gastroenterol. 2014 Feb 21;20(7):1635-49.
12 SEER Cancer Stat Facts: Stomach Cancer. Accessed May 2021.
13 Cancer Research UK. Stomach Cancer Survival Statistics. Accessed May 2021.
SOURCE: Daiichi Sankyo
