Phase Ib Study of the Safety of T-DXd and Immunotherapy Agents With and Without Chemotherapy in Advanced or Metastatic HER2+, Non-squamous NSCLC

Inclusion criteria: * Histologically documented unresectable locally advanced/metastatic non-squamous NSCLC * Part 1: Progression after 1 or 2 lines of systemic therapy for recurrent or metastatic setting. * Part 3, Part 4 and Part 5: Patients must have tumors that do not harbor known genomic alterations or actionable driver kinases, for which approved therapies are available are allowed. * Part 3, Part 4 and Part 5: Patient must be treatment-naïve for advanced or metastatic NSCLC. Patients who have received prior adjuvant, or neoadjuvant chemotherapy, or definitive chemoradiation for advanced disease are eligible, provided that progression has occurred \> 6 months from end of last therapy * HER2overexpression status as determined by central review of tumor tissue * WHO / ECOG performance status of 0 or 1 * Measurable target disease assessed by the investigator using RECIST 1.1 * Has protocol defined adequate organ and bone marrow function * Part 3, Part 4 and Part 5: Minimum body weight of 35 kg. Exclusion criteria: * HER2 mutation if previously known * Has a 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 * Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder and prior pneumonectomy * Active primary immunodeficiency known HIV infection, or active chronic and resolved hepatit…