'1. Objective * Primary objective \- Median Intracranial Progression-free survival(icPFS) as defined by RANO(Response Assessment in Neuro-Oncology) criteria * Secondary objective * Progression free survival(PFS) as defined by RECIST 1.1 * Median Intracranial progression free survival(icPFS) as defined by RECIST 1.1 * Intracranial objective response rate(icORR) as defined by RECIST 1.1 * Overall response rate(ORR) as defined by RECIST 1.1 * Duration of response(DoR) as defined by RECIST 1.1 * Disease control rate (DCR) defined by RECIST 1.1 * Overall survival (OS) ; The time from the date of inital IP administration to death due to any cause * Pattern of Progression ; Site of next progression * Safety objective * To evaluate the safety and tolerability of Trastuzumab deruxtecan.(AEs/SAEs, Vital signs, Collection of clinical chemistry/haematology parameters, ECGs) 2. Exploratory Purpose * To identify mechanisms of adaptive resistance using Guardant 360 panel. To conduct NGS using Guardant 360 panel in serial plasma collection before treatment and at the time of progression. * To identify the profiling of interstitial lung disease (ILD) after treatment of T-DXd. To perform the baseline and follow-up PFT. To perform high-resolution chest CT to evaluate for ILD by radiologic expert. To evaluate cytokine level in serially collected plasma (every 6 weeks for the first 24 weeks and then every 12 weeks). The investigators recommend doing one HRCT at baseline and a second one in the event of ILD. 3\. Background Human epidermal growth factor receptor 2 (HER2, ERBB2)-activating mutations occur in 2% of lung cancers as a distinct molecular target. HER2-targeted therapy is standard of care for HER2-mutation positive non-small cell lung cancer (NSCLC). Trastuzumab deruxtecan (T-DXd, DS-8201, Enhertu) is a novel antibody drug conjugate that is comprised of 3 components: a humanized anti-HER2 IgG1 monoclonal antibody with the same amino acid sequence as trastuzumab; a topoisomerase I inhibitor payload, an exatecan derivative; and a tetrapeptide-based cleavable linker. Recently, T-DXd induced a confirmed objective response rate (ORR) of almost 61% and a durable benefit in heavily pre-treated patients with advanced HER2-positive breast cancer, according to results from the phase II DESTINY-Breast01 trial. In addition, the DESTINY-Gastric trial showed the superiority of T-DXd compared with standard chemotherapy in terms of response rate and progression-free and overall survival in this setting. Altogether, T-DXd received breakthrough therapy designation and orphan drug designation in gastric cancer, and approval for the treatment of advanced HER2-positive breast cancer. Recently, T-DXd showed durable systemic disease control along with CNS response. Ongoing trials are assessing the activity of T-DXd in patients with breast cancer and active brain metastases. T-DXd has been approved in the US for the treatment of adult patients with unresectable or metastatic NSCLC whose tumours have activating HER2 mutations, as detected by a FDA-approved test, and who have received a prior systemic therapy. The accelerated approval by the FDA was based on the results from the DESTINY-Lung02 Phase II trial. An interim efficacy analysis in a pre-specified patient cohort showed T-DXd (5.4mg/kg) demonstrated a confirmed ORR of 57.7% (n=52; 95% CI 43.2-71.3), as assessed by blinded independent central review, in patients with previously treated unresectable or metastatic non-squamous HER2-mutant NSCLC. Complete responses (CR) were seen in 1.9% of patients and partial responses (PR) in 55.8% of patients with a median DoR of 8.7 months (95% CI 7.1-NE).
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Median Intracranial Progression-free survival(icPFS) as defined by RANO criteria
Timeframe: When all enrolled patients have completed 12 months of follow-up