A Study of T-DXd for the Treatment of Solid Tumors Harboring HER2 Activating Mutations

Inclusion Criteria: * Adults ≥18 years old. Other age restrictions may apply as per local regulations. * Unresectable and/or metastatic solid tumors with pre-specified HER2 mutations (S310F, S310Y, G660D, R678Q, D769Y, D769H, V777L, Y772\_A775dup / A775\_G776insYVMA, L755S, G778\_P780dup / P780\_Y781insGSP, T862A, and V842I locally determined by NGS or a validated nucleic acid-based methodology (eg, qPCR, digital PCR) on tumor tissue, who have progressed following prior treatment or who have no satisfactory alternative treatment options. * Prior HER2 targeted therapy is permitted. * All patients must provide an FFPE tumor sample for retrospective central HER2 testing. * LVEF ≥50% * ECOG 0-1 * All patients have measurable target disease assessed by the Investigator based on RECIST v1.1 Exclusion Criteria: * HER2 overexpressing (IHC3+ or IHC2+/ISH+) breast, gastric or gastroesophageal junction adenocarcinoma. * HER2 mutant NSCLC. * Medical history of myocardial infarction within 6 months before randomization/enrolment, symptomatic CHF, unstable angina pectoris, clinically important cardiac arrhythmias, or a recent (\< 6 months) cardiovascular event including stroke. * History of non-infectious pneumonitis/ILD, current ILD, or where suspected ILD cannot be ruled out by imaging at screening * Corrected QT interval by Fridericia's formula (QTcF) prolongation to \> 470 msec (females) or \> 450 msec (males) based on average of the screening triplicate 12-lead ECG. * Lung-specific intercurrent clinically significant severe illnesses. * History of active primary immunodeficiency, known HIV, active HBV or HCV infection * Uncontrolled infection requiring intravenous (IV) antibiotics, antivirals, or antifungals * Pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART). * Has spinal cord compression or clinically active central nervous system metastases.