HERTHENA-Lung01: Patritumab Deruxtecan in Subjects With Metastatic or Locally Advanced EGFR-mutated Non-Small Cell Lung Cancer

Participants must meet all of the following criteria to be eligible for inclusion in this study.

Sign and date the tissue informed consent form (ICF) and the main ICF, prior to the start of any study-specific qualification procedures.Male or female participants aged ≥18 years (follow local regulatory requirements if the legal age of consent for study participation is >18 years old). Histologically or cytologically documented locally advanced or metastatic NSCLC not amenable to curative surgery or radiation.

Documentation of radiological disease progression while on/after receiving most recent treatment regimen for locally advanced or metastatic disease. Participants must have received both of the following:

Prior treatment with osimertinib. Participants receiving an EGFR TKI at the time of signing informed consent should continue to take the EGFR TKI until 5 days prior to Cycle 1 Day 1. Participants in South Korea known to harbor a clinically actionable genomic alteration in addition to EGFR mutation (e.g., anaplastic lymphoma kinase [ALK] or ROS1 protocol oncogene 1 [ROS1] fusion) for which treatment is available must have also received prior treatment with at least 1 approved genotype-directed therapy, unless unable (i.e., if contraindicated). No new testing for these genomic alterations (e.g., ALK or ROS1 fusion) is required for Screening.Systemic therapy with at least 1 platinum-based chemotherapy regimen. Documentation of an EGFR-activating mutation detected from tumor tissue or blood sample: exon 19 deletion or L858R. At least 1 measurable lesion confirmed by BICR as per RECIST v1.1

Consented and willing to provide required tumor tissue of sufficient quantity and of adequate tumor tissue content. Required tumor tissue can be provided as either:

Pretreatment tumor biopsy from at least 1 lesion not previously irradiated and amenable to core biopsy ORArchival tumor tissue collected from a biopsy performed within 3 months prior to signing of the tissue consent and since progression while on or after treatment with the most recent cancer therapy regimen. Eastern Cooperative Oncology Group Performance Standard of 0 or 1 at Screening.

Has adequate bone marrow reserve and organ function based on local laboratory data within 14 days prior to Cycle 1 Day 1:

Platelet count : ≥100,000/mm^3 or ≥100 × 10^9/L (platelet transfusions are not allowed up to 14 days prior to Cycle 1 Day 1 to meet eligibility)Hemoglobin: ≥9.0 g/dL (transfusion and/or growth factor support is allowed) Absolute neutrophil count: ≥1500/mm^3 or ≥1.5 × 10^9/L Serum creatinine (SCr) or creatinine clearance (CrCl): SCr ≤1.5 × upper limit of normal (ULN), OR CrCl ≥30 mL/min as calculated using the Cockcroft-Gault equation or measured CrCl Aspartate aminotransferase/alanine aminotransferase: ≤3 × ULN (if liver metastases are present, ≤5 × ULN) Total bilirubin: ≤1.5 × ULN if no liver metastases (<3 × ULN in the presence of documented Gilbert's syndrome [unconjugated hyperbilirubinemia] or liver metastases) Serum albumin: ≥2.5 g/dL Prothrombin time (PT) or PT-International normalized ratio (INR) and activated partial thromboplastin time (aPTT)/PTT: ≤1.5 × ULN, except for subjects on coumarin-derivative anticoagulants or other similar anticoagulant therapy, who must have PT-INR within therapeutic range as deemed appropriate by the Investigator