A Single Arm Phase 2 Study to Evaluate Efficacy and Safety of Trastuzumab Deruxtecan for Patients With HER2 Mutant NSCLC

Inclusion Criteria: * Pathologically documented metastatic non-squamous NSCLC. * Has relapsed from or is refractory to at least one-line of anticancer treatment. * Documented HER2 exon 19 or 20 mutation from central FFPE tumour tissue testing. * WHO or ECOG performance status of 0 or 1. * Presence of at least one measurable lesion assessed by the investigator based on RECIST 1.1. * LVEF ≥ 50% within 28 days before enrolment. Exclusion Criteria: * Mixed small cell lung cancer, squamous histology NSCLC, and sarcomatoid histology variant NSCLC. * Corrected QT interval (QTcF) prolongation to \> 470 ms (females) or \> 450 ms (males), based on average of the screening triplicate 12-lead ECG. * History of (non-infectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at screening. * Has unresolved toxicities from previous anticancer therapy, defined as toxicities (excluding alopecia) not yet resolved to Grade ≤1 or baseline. Participants with clinically stable chronic Grade 2 toxicity not reasonably expected to be exacerbated by study intervention may be included only after consultation with the AstraZeneca study physician or designee. * Has been previously treated with HER2-targeted therapies, except for pan-HER class TKIs or has received prior treatment with an ADC which consists of an exatecan derivative that is a topoisomerase I inhibitor.