Based on pivotal DESTINY-Lung01 results showing
If approved, Enhertu to provide patients with a much-needed targeted therapy option
Enhertu is a HER2-directed antibody drug conjugate (ADC) being jointly developed by
The
Lung cancer is the second most common form of cancer globally, with more than two million new cases diagnosed in 2020.2 For patients with metastatic NSCLC, prognosis is particularly poor, as only approximately 8% will live beyond five years after diagnosis.3 There are currently no HER2-directed therapies approved specifically for the treatment of HER2-mutant NSCLC,4 which occurs in approximately 2-4% of patients with non-squamous NSCLC.4,5
The sBLA is based on data from the registrational DESTINY-Lung01 Phase II trial published in
Primary results from previously-treated patients with HER2-mutations (cohort 2) of DESTINY-Lung01 demonstrated a confirmed objective response rate (ORR) of 54.9% (95% confidence interval [CI]: 44.2-65.4) in patients treated with Enhertu (6.4mg/kg) as assessed by independent central review (ICR). One (1.1%) complete response (CR) and 49 (53.8%) partial responses (PR) were observed.
A confirmed disease control rate (DCR) of 92.3% was seen with a reduction in tumour size observed in most patients. After a median follow-up of 13.1 months, the median duration of response (DoR) for Enhertu was 9.3 months. The median progression-free survival (PFS) was 8.2 months and the median overall survival (OS) was 17.8 months.
The safety profile of the most common adverse events with Enhertu in DESTINY-Lung01 was consistent with previous clinical trials with no new safety concerns identified.
Enhertu is being further assessed in a comprehensive clinical development programme evaluating efficacy and safety across multiple HER2-targetable cancers, including breast, gastric, lung and colorectal cancers.
Notes
HER2-mutant NSCLC
Lung cancer is the second most common form of cancer globally, with more than two million new cases diagnosed in 2020.2 In the US, lung cancer is the second most commonly diagnosed cancer, with more than 236,000 new cases expected in 2022.6 For patients with metastatic NSCLC, prognosis is particularly poor, as only approximately 8% will live beyond five years after diagnosis.3
HER2 is a tyrosine kinase receptor growth-promoting protein expressed on the surface of many types of tumours, including lung, breast, gastric and colorectal cancers. Certain HER2gene alterations (called HER2 mutations) have been identified in NSCLC as distinct molecular targets and have been reported in approximately 2-4% of patients with non-squamous NSCLC.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.7 HER2gene mutations have been independently associated with cancer cell growth and poor prognosis, with an increased incidence of brain metastases.8 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.4,9 Next generation sequencing has been utilised in the identification of HER2 (ERBB2) mutations.10
DESTINY-Lung01
DESTINY-Lung01 isa global Phase II, open-label, two-cohort trial evaluating the safety and efficacy of Enhertu in patients with HER2-mutant (6.4mg/kg) or HER2-overexpressing (defined as IHC3+ or IHC2+) [6.4mg/kg and 5.4mg/kg] unresectable and/or metastatic non-squamous NSCLC who had progressed after one or more systemic therapies. The primary endpoint is confirmed ORR by ICR. Key secondary endpoints include DoR, DCR, PFS, OS and safety. DESTINY-Lung01 enrolled approximately 180 patients at multiple sites, including
Enhertu
Enhertu is a HER2-directed ADC. Designed using
Enhertu (5.4mg/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 two or more prior anti-HER2-based regimens based on the results from the DESTINY-Breast01 trial.
Enhertu (6.4mg/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.
Enhertu development programme
A comprehensive development programme is underway globally, 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 are currently under review in
Enhertu also is currently under review in
The Company's comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including Tagrisso (osimertinib) and Iressa (gefitinib); Imfinzi (durvalumab) and tremelimumab; Enhertu and datopotamab deruxtecan in collaboration with
The Company's focus is on some of the most challenging cancers. It is through persistent innovation that
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References
1. FDA. Priority Review. Available at: https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review. Accessed
2. WHO.
3.
4. Liu S, et al. Targeting HER2 Aberrations in Non-Small Cell
5. Campbell, JD, et al. Distinct patterns of somatic genome alterations in lung adenocarcinomas and squamous cell carcinomas. Nature Genetics. 2016;48(6):607-16.
6.
7. Pillai RN, et al. HER2 mutations in lung adenocarcinomas: A report from the
8. Offin M, et al. Frequency and Outcomes of Brain Metastases in Patients With HER2-Mutant Lung Cancers. Cancer. 2019;125:4380-7.
9. Zhou J, et al. Clinical outcomes of patients with HER2-mutant advanced lung cancer: chemotherapies versus HER2-directed therapies. Ther Adv Med Oncol. 2020;12:1-9.
10. Hechtman J, et al. The Past, Present, and Future of HER2 (ERBB2) in Cancer: Approaches to Molecular Testing and an Evolving Role in Targeted Therapy. Cancer Cyto 2019; 127 (7): 428-431.
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