ENHERTU® Type II Variation Application Validated by EMA for the Treatment of HER2 Mutant Metastatic Non-Small Cell Lung Cancer
Submission based on DESTINY-Lung02 and DESTINY-Lung01 phase 2 trial results which showed
Daiichi Sankyoand AstraZeneca’s ENHERTU demonstrated a clinically meaningful tumor response
ENHERTU is a specifically engineered HER2 directed antibody drug conjugate (ADC) being jointly developed and commercialized by
Validation confirms that the application is complete and commences the scientific review process by the EMA’s Committee for Medicinal Products for Human Use. This application is based on data from the DESTINY-Lung02 phase 2 trial presented at the
“ENHERTU is the first HER2 directed medicine shown to have a clinically meaningful tumor response in patients with previously treated HER2 mutant metastatic non-small cell lung cancer based on the results of the DESTINY-Lung02 and DESTINY-Lung01 trials,” said
DESTINY-Lung02 is a global, randomized phase 2 trial evaluating the safety and efficacy of ENHERTU in patients with HER2 mutant metastatic NSCLC with disease recurrence or progression during or after at least one regimen of prior anticancer therapy that must have contained a platinum-based chemotherapy. Patients were randomized 2:1 to receive ENHERTU 5.4 mg/kg (Cohort 1; n=102) or ENHERTU 6.4 mg/kg (Cohort 2; n=50).
The primary endpoint of the trial is confirmed objective response rate (ORR) as assessed by blinded independent central review (BICR). Secondary endpoints include confirmed disease control rate (DCR), duration of response (DoR) and progression free survival (PFS) assessed by investigator and BICR, investigator-assessed overall survival (OS) and safety. DESTINY-Lung02 enrolled 152 patients at multiple sites, including
DESTINY-Lung01 is a global phase 2, open-label, two-cohort trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg or 6.4 mg/kg) in patients with HER2 mutant (cohort 2, n=91) or HER2 overexpressing (cohort 1 and 1a, n=90) (defined as immunohistochemistry (IHC) 3+ or IHC 2+) unresectable or metastatic non-squamous NSCLC relapsed from or refractory to standard treatment or for which no standard treatment is available.
The primary endpoint of the trial is confirmed ORR by independent central review (ICR). Key secondary endpoints include DoR, DCR, PFS, OS and safety. DESTINY-Lung01 enrolled 181 patients at multiple sites, including
About HER2 Mutant NSCLC
Lung cancer is the second most common form of cancer globally, with more than two million cases diagnosed in 2020.1 In
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumors, including lung, breast, gastric and colorectal cancers. Certain HER2 (ERBB2) gene alterations (called HER2 mutations) have been identified in patients with non-squamous NSCLC as a distinct molecular target, and occur in approximately 2% to 4% of patients with this type of lung cancer.4,5 While HER2 gene mutations can occur in a range of patients, they are more commonly found in patients with NSCLC who are younger, female and have never smoked.6HER2 gene mutations have been independently associated with cancer cell growth and poor prognosis, with an increased incidence of brain metastases.7 Next-generation sequencing has been utilized in the identification of HER2 (ERBB2) mutations.8,9
Although the role of anti-HER2 treatment is well established in breast and gastric cancers, there were no approved HER2 directed therapies in NSCLC prior to the accelerated
ENHERTU® (trastuzumab deruxtecan; fam-trastuzumab deruxtecan-nxki in the
ENHERTU (5.4 mg/kg) is approved in more than 40 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-Breast03trial. 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-Breast01trial.
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 and/or DESTINY-Gastric02 trial.
About the ENHERTU Clinical Development Program
A comprehensive global development program is underway evaluating the efficacy and safety of ENHERTU monotherapy across multiple HER2targetable cancers including breast, gastric, lung and colorectal cancers. Trials in combination with other anticancer treatments, such as immunotherapy, also are underway.
Regulatory applications for ENHERTU in breast, non-small cell lung and gastric cancers are currently under review in several countries.
About the DXd ADC Portfolio of
The DXd ADC portfolio of
Each ADC is designed using Daiichi Sankyo’s proprietary DXd ADC technology to target and deliver a cytotoxic payload inside cancer cells that express a specific cell surface antigen. Each ADC consists of a monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.
Datopotamab deruxtecan, ifinatamab deruxtecan, patritumab deruxtecan and DS-6000 are investigational medicines that have not been approved for any indication in any country. Safety and efficacy have not been established.
1 WHO. Cancer Today. 2020. Accessed
2 WHO. Fact Sheets:
4 Liu S, et al.
5 Riudavets M, et al. ESMO Open. 2021; 6(5): 100260.
6 Pillai RN, et al. Cancer. 2017;123:4099-105.
7 Offin M, et al.Cancer. 2019;125:4380-7.
8 Hechtman J, et al. Cancer Cyto. 2019; 127(7): 428-431.
9 Gulilat, M, et al, BMC Med.Gen2019. 12:81.
10 Zhou J, et al. Ther Adv Med Oncol. 2020;12.
11 Ren S, et al. ESMO Open. 2022; 1:7.
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