TOKYO, Japan & MUNICH, Germany & BASKING RIDGE, NJ, USA I December 23, 2021 I Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) today announced that the first patient was dosed in the global DESTINY-Lung04 phase 3 trial evaluating the efficacy and safety of ENHERTU® (trastuzumab deruxtecan), a HER2 directed antibody drug conjugate (ADC) being jointly developed by Daiichi Sankyo and AstraZeneca (LSE/STO/Nasdaq: AZN), as a first-line treatment in patients with HER2 mutant unresectable, locally advanced or metastatic non-squamous non-small cell lung cancer (NSCLC).
DESTINY-Lung04 is the first head-to-head trial in NSCLC evaluating ENHERTU as a first-line treatment compared to the standard of care (platinum-pemetrexed doublet chemotherapy in combination with pembrolizumab) in patients with unresectable, locally advanced or metastatic non-squamous NSCLC harboring a HER2 exon 19 or 20 mutation.
Lung cancer is the leading cause of cancer death, accounting for about one-fifth of all cancer deaths globally, with 80% to 85% classified as NSCLC.1,2,3 There are currently no medicines approved specifically for the treatment of HER2 mutant NSCLC, which affects approximately 2% to 4% of patients with non-squamous NSCLC.4,5 Current standard of care in the first-line metastatic setting of patients with HER2 mutant NSCLC is PD-1 or PD-L1 immunotherapy with or without platinum-based chemotherapy.6 While these treatment regimens can improve survival in NSCLC, approximately 40% to 60% of tumors do not respond to initial treatment and disease progression occurs, underscoring the need for additional treatment approaches.7,8,9,10,11
“The results seen in the DESTINY-Lung01 trial showed a robust and durable tumor response in previously-treated patients with HER2 mutant metastatic non-small cell lung cancer,” said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. “Based on these promising findings, we are conducting DESTINY-Lung04 to evaluate the potential of ENHERTU as an earlier line of therapy in this patient population.”
About DESTINY-Lung04
DESTINY-Lung04 is a global, randomized, open-label, phase 3 trial evaluating the efficacy and safety of ENHERTU (5.4 mg/kg) compared to standard of care (platinum-pemetrexed doublet chemotherapy in combination with pembrolizumab) in patients with unresectable, locally advanced or metastatic, non-squamous NSCLC harboring a HER2 exon 19 or 20 mutation.
Patients will be randomized 1:1 to receive either ENHERTU or standard of care. The primary endpoint of DESTINY-Lung04 is progression-free survival (PFS) as assessed by blinded independent central review (BICR). Secondary endpoints include overall survival, investigator-assessed PFS, overall response rate and duration of response as assessed by BICR and investigator, pharmacokinetics, patient-reported tolerability, immunogenicity and safety.
DESTINY-Lung04 will enroll approximately 264 patients at multiple sites across Asia, Europe, and North America. For more information about the trial, visit ClinicalTrials.gov.
About HER2 Mutant NSCLC
Lung cancer is the leading cause of cancer death, accounting 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.2
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 as distinct molecular targets and have been reported in approximately 2% to 4% of patients with non-squamous NSCLC.4,5 These HER2 gene mutations are predominantly seen in younger women, with no smoking history and have been independently associated with cancer cell growth and poor prognosis, with an increased incidence of brain metastases.4,12,13,14,15,16 The most common HER2 mutations are exon 20 insertions, found in 35% to 59% of all HER2 mutations in NSCLC, while exon 19 mutations represent approximately 16% of mutations.17,18,19 Although the role of anti-HER2 treatment is well established in breast and gastric cancers, HER2 is an emerging biomarker in NSCLC with no approved HER2 directed therapies.4,20
Current standard of care in the first-line treatment of patients with HER2 mutant metastatic NSCLC is PD-1 or PD-L1 immunotherapy with or without platinum-based chemotherapy.6,7 While these treatment regimens can improve survival in NSCLC, at least 40% to 60% of tumors do not respond to initial treatment and disease progression occurs, underscoring the need for additional treatment approaches.7,8,9,10,11
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 more than 30 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.
A supplemental New Drug Application is under review in Japan for the treatment of adult patients with HER2 positive unresectable or recurrent breast cancer previously treated with trastuzumab and a taxane, based on the results from the DESTINY-Breast03 trial.
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.
A Type II Variation is currently under review by the European Medicines Agency (EMA) for the treatment of adult patients with locally advanced or metastatic HER2 positive gastric or GEJ adenocarcinoma who have received a prior anti-HER2-based regimen.
ENHERTU is approved in the U.S. with Boxed WARNINGS for Interstitial Lung Disease and Embryo-Fetal Toxicity. For more information, please see the 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 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, as well as one of the targeted therapy advances of the year in non-small cell lung cancer (NSCLC), based on the interim results of the HER2 mutated cohort of the DESTINY-Lung01 trial.
In September 2021, ENHERTU received its fourth Breakthrough Therapy Designation in the U.S. for the treatment of adult patients with unresectable or metastatic HER2 positive breast cancer who have received one or more prior anti-HER2-based regimens.
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 the manufacturing and supply of ENHERTU and datopotamab deruxtecan.
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:
1World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Accessed September 2021.
2 ASCO. Cancer.net. Lung Cancer – Non-Small Cell. Accessed September 2021.
3 Cheema PK, et al. Curr Oncol. 2019;26(1):37-42.
4 Liu S, et al. Clin Cancer Res. 2018;24(11):2594-2604.
5 Campbell JD, et al. Nat Genet. 2016 Jun;48(6):607-16.
6 Planchard D, et al. ESMO Clinical Practice Guidelines. 2020.
7 Man J, et al. JNCI Cancer Spectrum. 2021;5(3):pkab012.
8 Paz-Ares L, et al. J Thorac Oncol. 2020 Oct;15(10):1657-1669.
9 Mok TSK, et al. Lancet. 2019 May 4;393(10183):1819-1830.
10 Rodríguez-Abreu D et al. Ann Onc. 2021 Jul;32(7):881-895.
11 Brahmer J.R. et al. KEYNOTE-024 5-year OS update. ESMO 2021 Virtual Congress; Abstract LBA51.
12 Stephens P, et al. Nature. 2004;431:525-6.
13 Mazières J, et al. J Clin Oncol. 2013;31:1997-2003.
14 Arcila ME, et al. Clin Cancer Res. 2012;18:4910-8.
15 Pillai RN, et al. Cancer. 2017;123:4099-105.
16 Offin M, et al. Cancer. 2019;125:4380-7.
17 Ou S-HI, et al. J Clin Oncol. 2019;37(15 Suppl):9063.
18 Wei XW, et al. Thorac Cancer. 2020;11(6): 1512-21.
19 Robichaux et al. Cancer Cell. 2019 Oct 14; 36(4): 444–457.e7.
20 Zhou J, et al. Ther Adv Med Oncol. 2020;12.
SOURCE: Daiichi Sankyo
