TOKYO, Japan & MUNICH,Germany & BASKING RIDGE, NJ, USA I March 29, 2021 I Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) and AstraZeneca today announced the first patient was dosed in DESTINY-Lung02, a global phase 2 trial evaluating the safety and efficacy of ENHERTU® (trastuzumab deruxtecan) in patients with HER2 mutated metastatic non-small cell lung cancer (NSCLC) with disease recurrence or progression during or after at least one prior platinum-containing treatment regimen.
Lung cancer is the leading cause of cancer death among both men and women, and accounts for about one-fifth of all cancer deaths globally, with 80 to 85% classified as NSCLC.1,2,3 For patients with metastatic disease, prognosis is particularly poor, as only approximately 6% live beyond five years after diagnosis.4 There are currently no medicines approved specifically for the treatment of HER2 mutated NSCLC, which affects approximately 2 to 4% of patients with NSCLC.5,6
“Identification of the HER2 mutation as a distinct molecular target in non-small cell lung cancer has opened up a new and exciting area of research. Our initial research of ENHERTU in the DESTINY-Lung01 trial has shown impressive early results in patients with HER2 mutated metastatic non-small cell lung cancer,” said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. “Building on these results, we are initiating the DESTINY-Lung02 trial to further explore the safety and efficacy of two different doses of ENHERTU in this specific type of non-small cell lung cancer.”
About DESTINY-Lung02
DESTINY-Lung02 is a global phase 2 trial evaluating the safety and efficacy of two doses (5.4 mg/kg or 6.4 mg/kg) of ENHERTU in patients with HER2 mutated 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 drug (second line or later).
Patients will be randomized in a 2:1 ratio to receive either the 5.4 mg/kg or 6.4 mg/kg dose of ENHERTU. The primary endpoint of the study is objective response rate (ORR), as assessed by blinded independent central review. Secondary endpoints include disease control rate, duration of response, progression-free survival, investigator-assessed ORR, overall survival, pharmacokinetics, time to response, quality of life and safety.
DESTINY-Lung02 will enroll approximately 150 patients at multiple sites including but not limited to North America, Europe and Asia-Pacific. For more information about the trial, visit ClinicalTrials.gov.
About HER2 Mutated NSCLC
Lung cancer is the leading cause of cancer death among both men and women and accounts for about one-fifth of all cancer deaths globally, with 80 to 85% classified as NSCLC. 1,2,3 For patients with metastatic disease, prognosis is particularly poor, as only approximately 6% will live beyond five years after diagnosis.4
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. HER2 gene alterations (called HER2 mutations) have been identified in NSCLC, specifically adenocarcinomas, as distinct molecular targets and have been reported in approximately 2% to 4% of patients with NSCLC.5,6 These HER2 gene mutations have been independently associated with cancer cell growth and poor prognosis.5
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 under accelerated approval in the U.S., under conditional marketing authorization in the EU and UK, and under the conditional early approval system in Japan 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.
ENHERTU is not currently approved in the U.S. or any region worldwide for the treatment of NSCLC.
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 and lung cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.
ENHERTU was recently highlighted in the ASCO Clinical Cancer Advances 2021 report as one of the targeted therapy advances of the year in NSCLC, based on the interim results of the HER2 mutated cohort of the DESTINY-Lung01 trial.
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 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 Cancer Enterprise
The mission of Daiichi Sankyo Cancer Enterprise is to leverage our world-class, innovative science and push beyond traditional thinking to create meaningful treatments for patients with cancer. We are dedicated to transforming science into value for patients, and this sense of obligation informs everything we do. Anchored by our DXd antibody drug conjugate (ADC) technology, our powerful 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 Berkeley, CA. For more information, please visit: www.DSCancerEnterprise.com.
About Daiichi Sankyo
Daiichi Sankyo Group is dedicated to the creation and supply of innovative pharmaceutical therapies to improve standards of care and address diversified, unmet medical needs of people globally by leveraging our world-class science and technology. With more than 100 years of scientific expertise and a presence in more than 20 countries, Daiichi Sankyo and its 15,000 employees around the world draw upon a rich legacy of innovation and a robust pipeline of promising new medicines to help people. In addition to a strong portfolio of medicines for cardiovascular diseases, under the Group’s 2025 Vision to become a “Global Pharma Innovator with Competitive Advantage in Oncology,” Daiichi Sankyo is primarily focused on providing novel therapies in oncology, as well as other research areas centered around rare diseases and immune disorders. For more information, please visit: www.daiichisankyo.com.
References:
1 World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Accessed February 2021.
2 ASCO. Cancer.net. Lung Cancer – Non-Small Cell. Accessed February 2021.
3 Cheema PK, et al. Curr Oncol. 2019;26(1):37-42.
4 ASCO. Cancer.net. Lung Cancer – Non-Small Cell: Statistics. Accessed March 2021.
5 Liu S et al. Clin Cancer Res. 2018;24(11):2594-2604.
6 Campbell JD, et al. Nat Genet. 2016 Jun;48(6):607-16.
SOURCE: Daiichi Sankyo
