Results from the primary analysis of the DESTINY-Lung02 Phase II trial showed Enhertu continued to demonstrate strong and durable tumour responses in previously treated patients with HER2-mutant unresectable and/or metastatic non-squamous non-small cell lung cancer (NSCLC).
These results, along with the first report on progression-free survival (PFS) and overall survival (OS), were presented today at the
Enhertu is a specifically engineered HER2-directed antibody drug conjugate (ADC) being jointly developed and commercialised by
At the primary analysis, a confirmed objective response rate (ORR) of 49.0% and 56.0% was seen in the 5.4mg/kg arm and 6.4mg/kg arm respectively, as assessed by blinded independent central review (BICR). The safety profile for both doses was consistent with the overall safety profile of Enhertu, with the 5.4mg/kg dose demonstrating a favourable safety profile in this patient population.
Secondary endpoint data were also encouraging, with Enhertu demonstrating a median PFS of 9.9 months and 15.4 months in the 5.4mg/kg and 6.4mg/kg arms respectively, as assessed by BICR. A median OS of 19.5 months was achieved in the 5.4mg/kg arm and not reached in the 6.4mg/kg arm at time of analysis.
In DESTINY-Lung02, no new safety signals were observed at either dose of Enhertu. Grade 3 or higher treatment-related treatment emergent adverse events (TEAEs) were lower with Enhertu 5.4mg/kg versus 6.4mg/kg, occurring in 38.6% and 58.0% of all patients, respectively. The most common Grade 3 or higher TEAEs were neutropenia (18.8% (5.4mg/kg); 36.0% (6.4mg/kg)) and anaemia (10.9% (5.4mg/kg); 16.0% (6.4mg/kg)).
There were 27 cases (12.9% in the 5.4mg/kg arm and 28% in the 6.4mg/kg arm) of treatment-related interstitial lung disease (ILD) or pneumonitis reported as determined by an independent adjudication committee. In the 5.4mg/kg arm, the majority of ILD cases were low Grade (Grade 1 or 2) (10.9%) with one Grade 3 event (1.0%), no Grade 4 events and one Grade 5 event (1.0%) observed. In the 6.4mg/kg arm, the majority of ILD cases were also low Grade (26.0%) with no Grade 3 or 4 events and one Grade 5 event (2.0%) reported.
Notes
HER2m NSCLC
Lung cancer is the second most common form of cancer globally, with more than two million patients diagnosed in 2020.1 Prognosis is particularly poor for patients with metastatic NSCLC, as only approximately 9% 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 tumours, 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 2-4% of patients with this type of lung cancer.3,4 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.5 HER2 gene mutations have been independently associated with cancer cell growth and poor prognosis, with an increased incidence of brain metastases.6 Next-generation sequencing has been utilised in the identification of HER2 (ERBB2) mutations.7,8
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 approvals of Enhertu by the Israel Ministry of Health (MOH) Pharmaceutical Division, the
DESTINY-Lung02
DESTINY-Lung02 is a global, randomised Phase II trial evaluating the safety and efficacy of Enhertu in patients with HER2m unresectable and/or 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 randomised 2:1 to receive Enhertu 5.4mg/kg (n=102) or Enhertu 6.4mg/kg (n=50).
The primary endpoint of the trial is confirmed ORR as assessed by BICR. Secondary endpoints include confirmed DCR, DoR and PFS assessed by investigator and BICR, OS and safety.
DESTINY-Lung02 enrolled 152 patients at multiple sites, including
Enhertu
Enhertu is a HER2-directed ADC. Designed using
Enhertu (5.4mg/kg) is approved in more than 50 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-Breast03 trial.
Enhertu (5.4mg/kg) is approved in more than 40 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH-) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.
Enhertu (5.4mg/kg) is approved in
Enhertu (6.4mg/kg) is approved in more than 30 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 trials.
Enhertu development programme
A comprehensive clinical development programme is underway globally, evaluating the efficacy and safety of Enhertu monotherapy across multiple HER2-targetable cancers. Trials in combination with other anticancer treatments, such as immunotherapy, are also underway.
The Company s focus is on some of the most challenging cancers. It is through persistent innovation that
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